Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003490780 | SCV004242073 | likely benign | not specified | 2023-12-08 | criteria provided, single submitter | clinical testing | Variant summary: FRAS1 c.11274C>A (p.His3758Gln) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 9.5e-05 in 1613922 control chromosomes, predominantly at a frequency of 0.002 within the African or African-American subpopulation in the gnomAD database. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 1.13 fold of the estimated maximal expected allele frequency for a pathogenic variant in FRAS1 causing Cryptophthalmos Syndrome phenotype (0.0018), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. c.11274C>A has been reported in the literature in the heterozygous state in one individual affected with unilateral renal agenesis, with no second variant reported (Saisawat_2012). This report does not provide unequivocal conclusions about association of the variant with Cryptophthalmos Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 21900877). No submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely benign. |
| Fulgent Genetics, |
RCV005036839 | SCV005669790 | uncertain significance | Fraser syndrome 1 | 2024-03-21 | criteria provided, single submitter | clinical testing | |
| Prevention |
RCV003980966 | SCV004786469 | uncertain significance | FRAS1-related disorder | 2024-02-13 | no assertion criteria provided | clinical testing | The FRAS1 c.11274C>A variant is predicted to result in the amino acid substitution p.His3758Gln. This variant has been reported using alternate nomenclature (c.11268C>A, p.H3757Q) in the heterozygous state in an individual with renal agenesis (Saisawat et al. 2012. PubMed ID: 21900877). However, a second variant was not identified, no additional studies were conducted to support causation, and FRAS1 is not known to cause autosomal dominant disease. This variant is reported in 0.18% of alleles in individuals of African descent in gnomAD, which is likely too common to be a primary cause of disease. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |