Submissions for variant NM_000057.4(BLM):c.4076+4T>G

gnomAD frequency: 0.00436  dbSNP: rs183176301

Total submissions: 18

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000193294	SCV000167196	benign	not specified	2013-10-24	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.
Eurofins Ntd Llc (ga)	RCV000193294	SCV000227748	benign	not specified	2016-06-09	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000193294	SCV000246800	benign	not specified	2020-04-28	criteria provided, single submitter	clinical testing
Invitae	RCV000232892	SCV000283146	benign	Bloom syndrome	2024-02-01	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003891654	SCV000301747	benign	BLM-related condition	2020-06-05	criteria provided, single submitter	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Ambry Genetics	RCV000569071	SCV000672873	likely benign	Hereditary cancer-predisposing syndrome	2018-09-16	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000588309	SCV000694479	benign	not provided	2016-06-12	criteria provided, single submitter	clinical testing	Variant summary: The c.4076+4T>G in a BLM gene is an intronic variant that alters a non-conserved nucleotide. 5/5 in silico tools via Alamut predict this variant to not affect normal splicing, however these predictions have yet to be confirmed by functional assay. The variant is present in control dataset of ExAC at a frequency of 0.0038 (458/119942 chrs tested, including 3 homozygous occurrences) which exceeds the estimated maximum allele frequency for a pathogenic allele in this gene (0.0035), suggesting that this variant is a likely polymorphism. The variant has been reported in affected with breast cancer in literature (Thompson_2012) without strong evidence of causality. Multiple clinical laboratories have classified the variant as "Benign. Taken together, the variant is classified as Benign.
GeneKor MSA	RCV000569071	SCV000821795	likely benign	Hereditary cancer-predisposing syndrome	2018-08-01	criteria provided, single submitter	clinical testing
Mendelics	RCV000232892	SCV000838990	likely benign	Bloom syndrome	2018-07-02	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000588309	SCV001149595	likely benign	not provided	2024-02-01	criteria provided, single submitter	clinical testing	BLM: BP4, BS2
Illumina Laboratory Services, Illumina	RCV000232892	SCV001279112	likely benign	Bloom syndrome	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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000193294	SCV002047140	benign	not specified	2021-05-21	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000232892	SCV002048010	benign	Bloom syndrome	2021-04-15	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000569071	SCV002533029	benign	Hereditary cancer-predisposing syndrome	2020-07-20	criteria provided, single submitter	curation
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000588309	SCV001809029	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000588309	SCV001929817	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000588309	SCV001970942	likely benign	not provided		no assertion criteria provided	clinical testing
Natera, Inc.	RCV000232892	SCV002090648	benign	Bloom syndrome	2018-04-02	no assertion criteria provided	clinical testing