Variant 13-20187624-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_004004.6(GJB2):c.*1277T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.998 in 152,320 control chromosomes in the GnomAD database, including 75,805 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 1.0 ( 75805 hom., cov: 32)

Failed GnomAD Quality Control

Consequence

GJB2
NM_004004.6 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:3

Conservation

PhyloP100: -1.31

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 13-20187624-A-G is Benign according to our data. Variant chr13-20187624-A-G is described in ClinVar as [Benign]. Clinvar id is 311353.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.994 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.*1277T>C		3_prime_UTR_variant	2/2	ENST00000382848.5
GJB2	XM_011535049.3 linkuse as main transcript	c.*1277T>C		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.*1277T>C		3_prime_UTR_variant	2/2	1	NM_004004.6	P1
GJB2	ENST00000382844.2 linkuse as main transcript	c.*1277T>C		3_prime_UTR_variant	1/1			P1

Frequencies

GnomAD3 genomes

AF:

0.998

AC:

151846

AN:

152202

Hom.:

75747

Cov.:

show subpopulations

Gnomad AFR

AF:

0.992

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.999

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

1.00

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

1.00

Gnomad NFE

AF:

1.00

Gnomad OTH

AF:

0.997

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

GnomAD4 genome

AF:

0.998

AC:

151963

AN:

152320

Hom.:

75805

Cov.:

AF XY:

0.998

AC XY:

74325

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.992

Gnomad4 AMR

AF:

0.999

Gnomad4 ASJ

AF:

1.00

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

1.00

Gnomad4 FIN

AF:

1.00

Gnomad4 NFE

AF:

1.00

Gnomad4 OTH

AF:

0.997

Alfa

AF:

0.999

Hom.:

8800

Bravo

AF:

0.997

Asia WGS

AF:

0.999

AC:

3475

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

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

-0.90

CADD

Benign

0.44

DANN

Benign

0.53

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