ClinVar Miner

Submissions for variant NM_032043.2(BRIP1):c.587A>G (p.Asn196Ser) (rs550707862)

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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000235147 SCV000150072 likely benign not specified 2018-01-02 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Ambry Genetics RCV000116163 SCV000184386 likely benign Hereditary cancer-predisposing syndrome 2019-04-04 criteria provided, single submitter clinical testing In silico models in agreement (benign);Subpopulation frequency in support of benign classification
Invitae RCV001082539 SCV000253631 benign Familial cancer of breast; Fanconi anemia, complementation group J 2020-12-04 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000586611 SCV000699731 likely benign not provided 2017-05-15 criteria provided, single submitter clinical testing Variant summary: The BRIP1 c.587A>G (p.Asn196Ser) variant involves the alteration of a non-conserved nucleotide. 5/5 in silico tools predict a benign outcome for this variant. This variant was found in 55/121326 control chromosomes, predominantly observed in the East Asian subpopulation at a frequency of 0.005904 (51/8638). This frequency is about 94 times the estimated maximal expected allele frequency of a pathogenic BRIP1 variant (0.0000625), suggesting this is likely a benign polymorphism found primarily in the populations of East Asian origin. The variant has been reported in three East Asian patients with breast cancer in the literature (Cao_2009, Kim_2016), without strong evidence for causality. Multiple clinical diagnostic laboratories/reputable databases have classified this variant as likely benign. Taken together, this variant is classified as "likely benign".
Color Health, Inc RCV000116163 SCV000910593 benign Hereditary cancer-predisposing syndrome 2015-04-06 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000586611 SCV001134033 benign not provided 2018-10-02 criteria provided, single submitter clinical testing
Cancer Genomics Group,Japanese Foundation For Cancer Research RCV001030546 SCV001193542 uncertain significance Hereditary breast and ovarian cancer syndrome 2019-05-01 criteria provided, single submitter research
Illumina Clinical Services Laboratory,Illumina RCV001127949 SCV001287317 likely benign Fanconi anemia, complementation group J 2017-11-07 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Leiden Open Variation Database RCV000235147 SCV001364462 benign not specified 2019-08-13 no assertion criteria provided curation Curator: Arleen D. Auerbach. Submitter to LOVD: Yukihide Momozawa.
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001356235 SCV001551349 likely benign Cancer of cervix no assertion criteria provided clinical testing The BRIP1 p.Asn196Ser variant was identified in 5 of 1236 proband chromosomes (frequency: 0.004) from individuals or families with breast cancer (Kim 2016, Liu 2017, Cao 2009). The variant was also identified in dbSNP (ID: rs550707862) as "With Likely benign allele", ClinVar (classified as likely benign by Invitae, Ambry Genetics, GeneDx, and Integrated Genetics). The variant was identified in control databases in 136 of 277096 chromosomes (1 homozygous) at a frequency of 0.0005 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: Other in 1 of 6462 chromosomes (freq: 0.0002), Latino in 2 of 34414 chromosomes (freq: 0.00006), European Non-Finnish in 2 of 126626 chromosomes (freq: 0.00002), East Asian in 123 of 18854 chromosomes (freq: 0.007), and South Asian in 8 of 30782 chromosomes (freq: 0.0003), while the variant was not observed in the African, Ashkenazi Jewish or European Finnish populations. The p.Asn196 residue is not conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein; however, this information is not predictive enough to rule out pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001356416 SCV001551578 likely benign Malignant tumor of breast no assertion criteria provided clinical testing The BRIP1 p.Asn196Ser variant was identified in 5 of 1236 proband chromosomes (frequency: 0.004) from individuals or families with breast cancer (Kim 2016, Liu 2017, Cao 2009). The variant was also identified in dbSNP (ID: rs550707862) as "With Likely benign allele", ClinVar (classified as likely benign by Invitae, Ambry Genetics, GeneDx, and Integrated Genetics). The variant was identified in control databases in 136 of 277096 chromosomes (1 homozygous) at a frequency of 0.0005 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: Other in 1 of 6462 chromosomes (freq: 0.0002), Latino in 2 of 34414 chromosomes (freq: 0.00006), European Non-Finnish in 2 of 126626 chromosomes (freq: 0.00002), East Asian in 123 of 18854 chromosomes (freq: 0.007), and South Asian in 8 of 30782 chromosomes (freq: 0.0003), while the variant was not observed in the African, Ashkenazi Jewish or European Finnish populations. The p.Asn196 residue is not conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein; however, this information is not predictive enough to rule out pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.

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