X-71216669-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000675368.1(GJB1):c.-608C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 109,893 control chromosomes in the GnomAD database, including 1,456 homozygotes. There are 5,409 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.18 (1456 hom., 5409 hem., cov: 21)
• Consequence: GJB1 ENST00000675368.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.475

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.256 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GJB1	NM_001097642.3	c.-17+1379C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GJB1	ENST00000675368.1	c.-608C>T		5_prime_UTR_variant	1/2			P1
GJB1	ENST00000374029.2	c.-17+1398C>T		intron_variant		5		P1
GJB1	ENST00000447581.2	c.-200+1379C>T		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.179 AC: 19690 AN: 109841 Hom.: 1451 Cov.: 21 AF XY: 0.168 AC XY: 5399 AN XY: 32141

Gnomad AFR AF: 0.261

Gnomad AMI AF: 0.0486

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.131

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.211

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.159

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.179 AC: 19704 AN: 109893 Hom.: 1456 Cov.: 21 AF XY: 0.168 AC XY: 5409 AN XY: 32205

Gnomad4 AFR AF: 0.261

Gnomad4 AMR AF: 0.130

Gnomad4 ASJ AF: 0.126

Gnomad4 EAS AF: 0.131

Gnomad4 SAS AF: 0.101

Gnomad4 FIN AF: 0.157

Gnomad4 NFE AF: 0.157

Gnomad4 OTH AF: 0.159

Alfa AF: 0.166 Hom.: 2958

Bravo AF: 0.182

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	1.5
Dann	Benign	0.68

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

Other links and lift over

dbSNP: rs11094200; hg19: chrX-70436519;