Variant 13-20187834-C-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_004004.6(GJB2):c.*1067G>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 0.871 in 152,268 control chromosomes in the GnomAD database, including 58,617 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.87 ( 58616 hom., cov: 33)

Exomes 𝑓: 1.0 ( 1 hom. )

Consequence

GJB2
NM_004004.6 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.0270

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]

GJB2 links:

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=-0.91).

BP6

Variant 13-20187834-C-A is Benign according to our data. Variant chr13-20187834-C-A is described in ClinVar as [Benign]. Clinvar id is 311357.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GJB2	NM_004004.6 linkuse as main transcript	c.*1067G>T		3_prime_UTR_variant	2/2	ENST00000382848.5
GJB2	XM_011535049.3 linkuse as main transcript	c.*1067G>T		3_prime_UTR_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GJB2	ENST00000382848.5 linkuse as main transcript	c.*1067G>T		3_prime_UTR_variant	2/2	1	NM_004004.6	P1
GJB2	ENST00000382844.2 linkuse as main transcript	c.*1067G>T		3_prime_UTR_variant	1/1			P1

Frequencies

GnomAD3 genomes

AF:

0.871

AC:

132470

AN:

152148

Hom.:

58580

Cov.:

show subpopulations

Gnomad AFR

AF:

0.697

Gnomad AMI

AF:

0.923

Gnomad AMR

AF:

0.909

Gnomad ASJ

AF:

0.912

Gnomad EAS

AF:

0.999

Gnomad SAS

AF:

0.963

Gnomad FIN

AF:

0.948

Gnomad MID

AF:

0.940

Gnomad NFE

AF:

0.936

Gnomad OTH

AF:

0.885

GnomAD4 exome

AF:

1.00

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

show subpopulations

Gnomad4 FIN exome

AF:

1.00

GnomAD4 genome

AF:

0.871

AC:

132563

AN:

152266

Hom.:

58616

Cov.:

AF XY:

0.873

AC XY:

64981

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.697

Gnomad4 AMR

AF:

0.909

Gnomad4 ASJ

AF:

0.912

Gnomad4 EAS

AF:

0.999

Gnomad4 SAS

AF:

0.963

Gnomad4 FIN

AF:

0.948

Gnomad4 NFE

AF:

0.936

Gnomad4 OTH

AF:

0.886

Alfa

AF:

0.918

Hom.:

11544

Bravo

AF:

0.860

Asia WGS

AF:

0.966

AC:

3358

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 12, 2021	- -

Ichthyosis, hystrix-like, with hearing loss

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Autosomal recessive nonsyndromic hearing loss 1A

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

Autosomal dominant nonsyndromic hearing loss 3A

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.77

DANN

Benign

0.47

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over