rs561870637
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6BP7
The NM_004004.6(GJB2):āc.120A>Cā(p.Ala40=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000157 in 1,613,546 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. A40A) has been classified as Likely benign.
Frequency
Consequence
NM_004004.6 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GJB2 | NM_004004.6 | c.120A>C | p.Ala40= | synonymous_variant | 2/2 | ENST00000382848.5 | |
GJB2 | XM_011535049.3 | c.120A>C | p.Ala40= | synonymous_variant | 2/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GJB2 | ENST00000382848.5 | c.120A>C | p.Ala40= | synonymous_variant | 2/2 | 1 | NM_004004.6 | P1 | |
GJB2 | ENST00000382844.2 | c.120A>C | p.Ala40= | synonymous_variant | 1/1 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000145 AC: 22AN: 152204Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000171 AC: 43AN: 250886Hom.: 0 AF XY: 0.000221 AC XY: 30AN XY: 135632
GnomAD4 exome AF: 0.000158 AC: 231AN: 1461224Hom.: 0 Cov.: 33 AF XY: 0.000172 AC XY: 125AN XY: 726782
GnomAD4 genome AF: 0.000144 AC: 22AN: 152322Hom.: 0 Cov.: 33 AF XY: 0.000121 AC XY: 9AN XY: 74482
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Oct 10, 2014 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | - - |
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Aug 28, 2019 | - - |
Likely benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Dec 24, 2018 | - - |
Autosomal recessive nonsyndromic hearing loss 1A Benign:2
Likely benign, no assertion criteria provided | clinical testing | Natera, Inc. | Feb 22, 2020 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | 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). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
Ichthyosis, hystrix-like, with hearing loss Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | 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. - |
Autosomal dominant nonsyndromic hearing loss 3A Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | 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). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at