13-20188733-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004004.6(GJB2):​c.*168A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0463 in 636,298 control chromosomes in the GnomAD database, including 851 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.040 ( 173 hom., cov: 33)
Exomes 𝑓: 0.048 ( 678 hom. )

Consequence

GJB2
NM_004004.6 3_prime_UTR

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -1.65
Variant links:
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 Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
Variant 13-20188733-T-C is Benign according to our data. Variant chr13-20188733-T-C is described in ClinVar as [Benign]. Clinvar id is 311369.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.059 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GJB2NM_004004.6 linkc.*168A>G 3_prime_UTR_variant Exon 2 of 2 ENST00000382848.5 NP_003995.2 P29033H9U1J4
GJB2XM_011535049.3 linkc.*168A>G 3_prime_UTR_variant Exon 2 of 2 XP_011533351.1 P29033H9U1J4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GJB2ENST00000382848 linkc.*168A>G 3_prime_UTR_variant Exon 2 of 2 1 NM_004004.6 ENSP00000372299.4 P29033
GJB2ENST00000382844 linkc.*168A>G 3_prime_UTR_variant Exon 1 of 1 ENSP00000372295.1 P29033

Frequencies

GnomAD3 genomes
AF:
0.0400
AC:
6095
AN:
152232
Hom.:
173
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0108
Gnomad AMI
AF:
0.00439
Gnomad AMR
AF:
0.0473
Gnomad ASJ
AF:
0.0352
Gnomad EAS
AF:
0.00519
Gnomad SAS
AF:
0.0250
Gnomad FIN
AF:
0.0387
Gnomad MID
AF:
0.0570
Gnomad NFE
AF:
0.0605
Gnomad OTH
AF:
0.0497
GnomAD4 exome
AF:
0.0483
AC:
23397
AN:
483948
Hom.:
678
Cov.:
4
AF XY:
0.0472
AC XY:
12168
AN XY:
257894
show subpopulations
Gnomad4 AFR exome
AF:
0.0103
Gnomad4 AMR exome
AF:
0.0383
Gnomad4 ASJ exome
AF:
0.0373
Gnomad4 EAS exome
AF:
0.00744
Gnomad4 SAS exome
AF:
0.0254
Gnomad4 FIN exome
AF:
0.0423
Gnomad4 NFE exome
AF:
0.0605
Gnomad4 OTH exome
AF:
0.0491
GnomAD4 genome
AF:
0.0400
AC:
6094
AN:
152350
Hom.:
173
Cov.:
33
AF XY:
0.0385
AC XY:
2869
AN XY:
74508
show subpopulations
Gnomad4 AFR
AF:
0.0108
Gnomad4 AMR
AF:
0.0472
Gnomad4 ASJ
AF:
0.0352
Gnomad4 EAS
AF:
0.00520
Gnomad4 SAS
AF:
0.0251
Gnomad4 FIN
AF:
0.0387
Gnomad4 NFE
AF:
0.0605
Gnomad4 OTH
AF:
0.0497
Alfa
AF:
0.0523
Hom.:
58
Bravo
AF:
0.0390
Asia WGS
AF:
0.0150
AC:
51
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Autosomal recessive nonsyndromic hearing loss 1A Benign:2
Jul 01, 2021
Pars Genome Lab
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Apr 27, 2017
Illumina Laboratory Services, Illumina
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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 was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -

not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Oct 22, 2018
GeneDx
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Autosomal dominant nonsyndromic hearing loss 3A Benign:2
Apr 27, 2017
Illumina Laboratory Services, Illumina
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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 was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -

Jul 01, 2021
Pars Genome Lab
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Ichthyosis, hystrix-like, with hearing loss Benign:1
Apr 27, 2017
Illumina Laboratory Services, Illumina
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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 was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.85
CADD
Benign
0.041
DANN
Benign
0.51

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs55704559; hg19: chr13-20762872; API