Variant 1-34761362-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_153212.3(GJB4):c.108C>T(p.Tyr36=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00555 in 1,614,030 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0042 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0057 ( 26 hom. )

Consequence

GJB4
NM_153212.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.866

Variant links:

Genes affected

GJB4 (HGNC:4286): (gap junction protein beta 4) This gene encodes a transmembrane connexin protein that is a component of gap junctions. Mutations in this gene have been associated with erythrokeratodermia variabilis, progressive symmetric erythrokeratoderma and hearing impairment. [provided by RefSeq, Dec 2009]

GJB4 links:

SMIM12 (HGNC:25154): (small integral membrane protein 12) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

SMIM12 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 1-34761362-C-T is Benign according to our data. Variant chr1-34761362-C-T is described in ClinVar as [Benign]. Clinvar id is 710496.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.866 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00419 (638/152312) while in subpopulation AMR AF= 0.00699 (107/15300). AF 95% confidence interval is 0.00592. There are 2 homozygotes in gnomad4. There are 286 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd at 638 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GJB4	NM_153212.3 linkuse as main transcript	c.108C>T	p.Tyr36=	synonymous_variant	2/2	ENST00000339480.3
GJB4	XM_011540679.3 linkuse as main transcript	c.108C>T	p.Tyr36=	synonymous_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GJB4	ENST00000339480.3 linkuse as main transcript	c.108C>T	p.Tyr36=	synonymous_variant	2/2	2	NM_153212.3	P1
SMIM12	ENST00000426886.1 linkuse as main transcript	c.208-42953G>A		intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes

AF:

0.00419

AC:

638

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00142

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.00700

Gnomad ASJ

AF:

0.00404

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.00113

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00620

Gnomad OTH

AF:

0.00573

GnomAD3 exomes

AF:

0.00431

AC:

1083

AN:

251382

Hom.:

AF XY:

0.00453

AC XY:

615

AN XY:

135866

show subpopulations

Gnomad AFR exome

AF:

0.000861

Gnomad AMR exome

AF:

0.00347

Gnomad ASJ exome

AF:

0.00576

Gnomad EAS exome

AF:

0.000435

Gnomad SAS exome

AF:

0.000751

Gnomad FIN exome

AF:

0.00245

Gnomad NFE exome

AF:

0.00687

Gnomad OTH exome

AF:

0.00423

GnomAD4 exome

AF:

0.00570

AC:

8327

AN:

1461718

Hom.:

Cov.:

AF XY:

0.00557

AC XY:

4051

AN XY:

727170

show subpopulations

Gnomad4 AFR exome

AF:

0.000627

Gnomad4 AMR exome

AF:

0.00353

Gnomad4 ASJ exome

AF:

0.00497

Gnomad4 EAS exome

AF:

0.000252

Gnomad4 SAS exome

AF:

0.000997

Gnomad4 FIN exome

AF:

0.00313

Gnomad4 NFE exome

AF:

0.00668

Gnomad4 OTH exome

AF:

0.00515

GnomAD4 genome

AF:

0.00419

AC:

638

AN:

152312

Hom.:

Cov.:

AF XY:

0.00384

AC XY:

286

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.00142

Gnomad4 AMR

AF:

0.00699

Gnomad4 ASJ

AF:

0.00404

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000828

Gnomad4 FIN

AF:

0.00113

Gnomad4 NFE

AF:

0.00620

Gnomad4 OTH

AF:

0.00567

Alfa

AF:

0.00552

Hom.:

Bravo

AF:

0.00431

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00698

EpiControl

AF:

0.00765

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 17, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

Cadd

Benign

5.4

Dann

Benign

0.74

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