ClinVar Miner

Submissions for variant NM_000414.4(HSD17B4):c.420A>T (p.Lys140Asn)

gnomAD frequency: 0.02134  dbSNP: rs28943589
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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000221723 SCV000269166 benign not specified 2014-11-24 criteria provided, single submitter clinical testing Lys165Asn in exon 8 of HSD17B4: This variant is not expected to have clinical si gnificance because it has been identified in 6.1% (268/4404) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http ://evs.gs.washington.edu/EVS; dbSNP rs28943589).
PreventionGenetics, part of Exact Sciences RCV000221723 SCV000304080 benign not specified criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000309262 SCV000452109 benign Bifunctional peroxisomal enzyme deficiency 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Laboratory Services, Illumina RCV000368516 SCV000452110 benign Perrault syndrome 1 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Invitae RCV001084537 SCV000636111 benign Bifunctional peroxisomal enzyme deficiency; Perrault syndrome 2024-01-31 criteria provided, single submitter clinical testing
GeneDx RCV000221723 SCV000729828 benign not specified 2017-09-18 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.
Athena Diagnostics RCV000711976 SCV000842389 benign not provided 2018-05-24 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000711976 SCV001472909 benign not provided 2023-11-29 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000221723 SCV001519622 benign not specified 2021-03-15 criteria provided, single submitter clinical testing Variant summary: HSD17B4 c.420A>T (p.Lys140Asn) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.006 in 251368 control chromosomes in the gnomAD database, including 46 homozygotes. The observed variant frequency is approximately 2.0 fold of the estimated maximal expected allele frequency for a pathogenic variant in HSD17B4 causing D-Bifunctional Protein Deficiency phenotype (0.003), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.420A>T in individuals affected with D-Bifunctional Protein Deficiency and no experimental evidence demonstrating its impact on protein function have been reported. Six clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign. Based on the evidence outlined above, the variant was classified as benign.
Natera, Inc. RCV000309262 SCV001457635 benign Bifunctional peroxisomal enzyme deficiency 2020-09-16 no assertion criteria provided clinical testing

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