Variant X-71223451-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000166.6(GJB1):c.-17+116C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0204 in 436,540 control chromosomes in the GnomAD database, including 95 homozygotes. There are 2,722 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.024 ( 41 hom., 648 hem., cov: 23)

Exomes 𝑓: 0.019 ( 54 hom. 2074 hem. )

Consequence

GJB1
NM_000166.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.119

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant X-71223451-C-T is Benign according to our data. Variant chrX-71223451-C-T is described in ClinVar as [Benign]. Clinvar id is 380814.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-71223451-C-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0238 (2623/110429) while in subpopulation AFR AF= 0.0374 (1136/30341). AF 95% confidence interval is 0.0356. There are 41 homozygotes in gnomad4. There are 648 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 41 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
GJB1	NM_000166.6 linkuse as main transcript	c.-17+116C>T	intron_variant	ENST00000361726.7
GJB1	NM_001097642.3 linkuse as main transcript	c.-16-241C>T	intron_variant
GJB1	XM_011530907.3 linkuse as main transcript	c.-16-241C>T	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GJB1	ENST00000361726.7 linkuse as main transcript	c.-17+116C>T		intron_variant		1	NM_000166.6	P1

Frequencies

GnomAD3 genomes

AF:

0.0238

AC:

2625

AN:

110380

Hom.:

Cov.:

AF XY:

0.0198

AC XY:

648

AN XY:

32686

show subpopulations

Gnomad AFR

AF:

0.0375

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0149

Gnomad ASJ

AF:

0.0566

Gnomad EAS

AF:

0.000566

Gnomad SAS

AF:

0.00724

Gnomad FIN

AF:

0.00659

Gnomad MID

AF:

0.0565

Gnomad NFE

AF:

0.0204

Gnomad OTH

AF:

0.0258

GnomAD4 exome

AF:

0.0193

AC:

6303

AN:

326111

Hom.:

AF XY:

0.0188

AC XY:

2074

AN XY:

110139

show subpopulations

Gnomad4 AFR exome

AF:

0.0458

Gnomad4 AMR exome

AF:

0.0123

Gnomad4 ASJ exome

AF:

0.0553

Gnomad4 EAS exome

AF:

0.0000440

Gnomad4 SAS exome

AF:

0.00739

Gnomad4 FIN exome

AF:

0.0108

Gnomad4 NFE exome

AF:

0.0207

Gnomad4 OTH exome

AF:

0.0259

GnomAD4 genome

AF:

0.0238

AC:

2623

AN:

110429

Hom.:

Cov.:

AF XY:

0.0198

AC XY:

648

AN XY:

32747

show subpopulations

Gnomad4 AFR

AF:

0.0374

Gnomad4 AMR

AF:

0.0149

Gnomad4 ASJ

AF:

0.0566

Gnomad4 EAS

AF:

0.000568

Gnomad4 SAS

AF:

0.00726

Gnomad4 FIN

AF:

0.00659

Gnomad4 NFE

AF:

0.0204

Gnomad4 OTH

AF:

0.0255

Alfa

AF:

0.0126

Hom.:

Bravo

AF:

0.0263

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 01, 2016

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

1.1

DANN

Benign

0.78

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