Variant X-71223079-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2

The NM_001097642.3(GJB1):c.-16-613C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00645 in 118,842 control chromosomes in the GnomAD database, including 7 homozygotes. There are 208 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0068 ( 7 hom., 206 hem., cov: 22)

Exomes 𝑓: 0.00086 ( 0 hom. 2 hem. )

Consequence

GJB1
NM_001097642.3 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.08

Variant links:

Genes affected

GJB1 (HGNC:4283): (gap junction protein beta 1) This gene encodes a member of the gap junction protein family. The gap junction proteins are membrane-spanning proteins that assemble to form gap junction channels that facilitate the transfer of ions and small molecules between cells. 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 cause X-linked Charcot-Marie-Tooth disease, an inherited peripheral neuropathy. Alternatively spliced transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Oct 2008]

GJB1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP6

Variant X-71223079-C-T is Benign according to our data. Variant chrX-71223079-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1203086.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0068 (761/111899) while in subpopulation AFR AF= 0.023 (709/30800). AF 95% confidence interval is 0.0216. There are 7 homozygotes in gnomad4. There are 206 alleles in male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 7 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GJB1	NM_001097642.3 linkuse as main transcript	c.-16-613C>T		intron_variant
GJB1	XM_011530907.3 linkuse as main transcript	c.-17+313C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	Appris
GJB1	ENST00000374029.2 linkuse as main transcript	c.-16-613C>T	intron_variant	5	P1
GJB1	ENST00000447581.2 linkuse as main transcript	c.-17+313C>T	intron_variant	5	P1
GJB1	ENST00000645009.2 linkuse as main transcript	c.-16-613C>T	intron_variant		P1

Frequencies

GnomAD3 genomes

AF:

0.00680

AC:

761

AN:

111846

Hom.:

Cov.:

AF XY:

0.00605

AC XY:

206

AN XY:

34036

show subpopulations

Gnomad AFR

AF:

0.0231

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00275

Gnomad ASJ

AF:

0.000378

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000162

Gnomad MID

AF:

0.00420

Gnomad NFE

AF:

0.000170

Gnomad OTH

AF:

0.00724

GnomAD4 exome

AF:

0.000864

AC:

AN:

6943

Hom.:

AF XY:

0.00136

AC XY:

AN XY:

1471

show subpopulations

Gnomad4 AFR exome

AF:

0.0301

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00292

GnomAD4 genome

AF:

0.00680

AC:

761

AN:

111899

Hom.:

Cov.:

AF XY:

0.00604

AC XY:

206

AN XY:

34099

show subpopulations

Gnomad4 AFR

AF:

0.0230

Gnomad4 AMR

AF:

0.00275

Gnomad4 ASJ

AF:

0.000378

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000162

Gnomad4 NFE

AF:

0.000170

Gnomad4 OTH

AF:

0.00715

Alfa

AF:

0.00744

Hom.:

Bravo

AF:

0.00805

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 21, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Benign

0.89

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