rs115293759
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_017780.4(CHD7):c.309G>A(p.Ser103=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000941 in 1,613,900 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. S103S) has been classified as Likely benign.
Frequency
Consequence
NM_017780.4 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CHD7 | NM_017780.4 | c.309G>A | p.Ser103= | synonymous_variant | 2/38 | ENST00000423902.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHD7 | ENST00000423902.7 | c.309G>A | p.Ser103= | synonymous_variant | 2/38 | 5 | NM_017780.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00539 AC: 820AN: 152170Hom.: 6 Cov.: 32
GnomAD3 exomes AF: 0.00131 AC: 326AN: 248938Hom.: 4 AF XY: 0.000903 AC XY: 122AN XY: 135072
GnomAD4 exome AF: 0.000478 AC: 699AN: 1461612Hom.: 4 Cov.: 32 AF XY: 0.000400 AC XY: 291AN XY: 727088
GnomAD4 genome ? AF: 0.00538 AC: 819AN: 152288Hom.: 6 Cov.: 32 AF XY: 0.00498 AC XY: 371AN XY: 74462
ClinVar
Submissions by phenotype
not specified Benign:8
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Aug 28, 2019 | - - |
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Sep 26, 2013 | - - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Aug 23, 2017 | p.Ser103Ser in exon 2 of CHD7: This variant is not expected to have clinical significance because it does not alter an amino acid residue, is not located within the splice consensus sequence, and has been identified in 1.89% (183/9668) of African chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs115293759). - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 22, 2016 | 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. - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Inborn genetic diseases Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 01, 2016 | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, 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. - |
CHARGE association;C3552553:Hypogonadotropic hypogonadism 5 with or without anosmia Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Jul 30, 2021 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Jun 27, 2016 | Variant summary: The CHD7 c.309G>A (p.Ser103Ser) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a damaging outcome for this variant, but 5/5 splicing algorithms predict no significant change to normal splicing. This variant was found in 199/119626 control chromosomes (3 homozygotes) at a frequency of 0.0016635, which is approximately 1331 times the estimated maximal expected allele frequency of a pathogenic CHD7 variant (0.0000013), suggesting this variant is likely a benign polymorphism. The variant has been cited in at least one CHARGE syndrome patient in the literature without evidence of causality (Jain_Int J Pediatr Endocrinol_2011). In addition, one clinical diagnostic laboratory classified this variant as benign. Based on the synonymous nature of this variant and the high allele frequency in the general population, this variant was classified as benign. - |
CHARGE association Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 30, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at