rs111033327
Positions:
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP6
The NM_004004.6(GJB2):c.*1C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000393 in 1,611,446 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: 𝑓 0.00049 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00038 ( 0 hom. )
Consequence
GJB2
NM_004004.6 3_prime_UTR
NM_004004.6 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0700
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BP6
?
Variant 13-20188900-G-A is Benign according to our data. Variant chr13-20188900-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 44715.We mark this variant Likely_benign, oryginal submissions are: {Benign=2, Uncertain_significance=2, Likely_benign=7}. Variant chr13-20188900-G-A is described in Lovd as [Likely_benign].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GJB2 | NM_004004.6 | c.*1C>T | 3_prime_UTR_variant | 2/2 | ENST00000382848.5 | ||
GJB2 | XM_011535049.3 | c.*1C>T | 3_prime_UTR_variant | 2/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GJB2 | ENST00000382848.5 | c.*1C>T | 3_prime_UTR_variant | 2/2 | 1 | NM_004004.6 | P1 | ||
GJB2 | ENST00000382844.2 | c.*1C>T | 3_prime_UTR_variant | 1/1 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000486 AC: 74AN: 152194Hom.: 0 Cov.: 33
GnomAD3 genomes
?
AF:
AC:
74
AN:
152194
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000538 AC: 133AN: 247376Hom.: 0 AF XY: 0.000609 AC XY: 82AN XY: 134560
GnomAD3 exomes
AF:
AC:
133
AN:
247376
Hom.:
AF XY:
AC XY:
82
AN XY:
134560
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000383 AC: 559AN: 1459134Hom.: 0 Cov.: 31 AF XY: 0.000355 AC XY: 258AN XY: 726018
GnomAD4 exome
AF:
AC:
559
AN:
1459134
Hom.:
Cov.:
31
AF XY:
AC XY:
258
AN XY:
726018
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.000486 AC: 74AN: 152312Hom.: 0 Cov.: 33 AF XY: 0.000524 AC XY: 39AN XY: 74484
GnomAD4 genome
?
AF:
AC:
74
AN:
152312
Hom.:
Cov.:
33
AF XY:
AC XY:
39
AN XY:
74484
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:3Benign:9
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1Benign:3
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Oct 27, 2014 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 22, 2019 | This variant is associated with the following publications: (PMID: 20022641, 17666888, 22567369, 15744158, 17041943) - |
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | May 31, 2016 | - - |
Likely benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Aug 21, 2019 | - - |
Autosomal recessive nonsyndromic hearing loss 1A Uncertain:2Benign:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | May 19, 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | May 24, 2018 | - - |
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Feb 08, 2013 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jun 03, 2011 | The *1C>T variant was identified in the 3?UTR of GJB2. This variant is located 1 base after the termination codon. Although, this variant has been detected in i ndividuals with hearing loss, it has never been identified with a second pathoge nic GJB2 variant (Frei 2005, Samanich 2007, Tang 2006, Rabionet unpublished). In addition, it was identified at an equal frequency (0.5%) in control chromosomes (Samanich 2007). In summary, the *1C>T variant is not expected to have clinical or pathological significance because it is not predicted to affect the transcri pt and has been found at an equal frequency in controls. - |
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. - |
Nonsyndromic genetic hearing loss Benign:1
Likely benign, criteria provided, single submitter | clinical testing | INGEBI, INGEBI / CONICET | Aug 31, 2020 | Based on ACMG/AMP guidelines and Hearing Loss Expert Panel specific criteria: the filtering allele frequency of the c.*1C>T variant in GJB2 gene is 0,16% in latino population (72/35366 alleles with 95%CI) from Genome Aggregation Database (http://gnomad.broadinstitute.org; calculated by using inverse allele frequency at https://www.cardiodb.org/allelefrequencyapp/), which meets the BS1_Supporting rule. Bening computational veredict prediction from DANN and CADD predictors applying for BP4 rule. In summary, the c.*1C>T variant meets criteria to be classified likely benign (BS1_Supporting, BP4) - |
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:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at