rs561870637
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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.Ala40Ala) 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).
Frequency
Genomes: š 0.00014 ( 0 hom., cov: 33)
Exomes š: 0.00016 ( 0 hom. )
Consequence
GJB2
NM_004004.6 synonymous
NM_004004.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -9.42
Genes affected
GJB2 (HGNC:4284): (gap junction protein beta 2) This gene encodes a member of the gap junction protein family. The gap junctions were first characterized by electron microscopy as regionally specialized structures on plasma membranes of contacting adherent cells. These structures were shown to consist of cell-to-cell channels that facilitate the transfer of ions and small molecules between cells. The gap junction proteins, also known as connexins, purified from fractions of enriched gap junctions from different tissues differ. According to sequence similarities at the nucleotide and amino acid levels, the gap junction proteins are divided into two categories, alpha and beta. Mutations in this gene are responsible for as much as 50% of pre-lingual, recessive deafness. [provided by RefSeq, Oct 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-1.02).
BP6
Variant 13-20189462-T-G is Benign according to our data. Variant chr13-20189462-T-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 195206.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=6, Uncertain_significance=1}.
BP7
Synonymous conserved (PhyloP=-9.42 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GJB2 | NM_004004.6 | c.120A>C | p.Ala40Ala | synonymous_variant | 2/2 | ENST00000382848.5 | NP_003995.2 | |
GJB2 | XM_011535049.3 | c.120A>C | p.Ala40Ala | synonymous_variant | 2/2 | XP_011533351.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GJB2 | ENST00000382848.5 | c.120A>C | p.Ala40Ala | synonymous_variant | 2/2 | 1 | NM_004004.6 | ENSP00000372299.4 | ||
GJB2 | ENST00000382844.2 | c.120A>C | p.Ala40Ala | synonymous_variant | 1/1 | 6 | ENSP00000372295.1 |
Frequencies
GnomAD3 genomes AF: 0.000145 AC: 22AN: 152204Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000171 AC: 43AN: 250886Hom.: 0 AF XY: 0.000221 AC XY: 30AN XY: 135632
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GnomAD4 exome AF: 0.000158 AC: 231AN: 1461224Hom.: 0 Cov.: 33 AF XY: 0.000172 AC XY: 125AN XY: 726782
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GnomAD4 genome AF: 0.000144 AC: 22AN: 152322Hom.: 0 Cov.: 33 AF XY: 0.000121 AC XY: 9AN XY: 74482
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:7
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 25, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Oct 10, 2014 | - - |
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
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at