X-71221881-A-T

Position:

• chrX-71221881-A-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001097642.3(GJB1):​c.-16-1811A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.68 (18820 hom., 20443 hem., cov: 21)
  • Failed GnomAD Quality Control
• Consequence: GJB1 NM_001097642.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.171

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 Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GJB1	NM_001097642.3	c.-16-1811A>T		intron_variant			NP_001091111.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GJB1	ENST00000374029.2	c.-16-1811A>T		intron_variant		5		ENSP00000363141	P1
GJB1	ENST00000447581.2	c.-199-703A>T		intron_variant		5		ENSP00000407223	P1
GJB1	ENST00000645009.2	c.-16-1811A>T		intron_variant				ENSP00000494142	P1

Frequencies

GnomAD3 genomes AF: 0.684 AC: 73790 AN: 107858 Hom.: 18809 Cov.: 21 AF XY: 0.674 AC XY: 20386 AN XY: 30260

Gnomad AFR AF: 0.840

Gnomad AMI AF: 0.653

Gnomad AMR AF: 0.676

Gnomad ASJ AF: 0.562

Gnomad EAS AF: 0.772

Gnomad SAS AF: 0.586

Gnomad FIN AF: 0.616

Gnomad MID AF: 0.597

Gnomad NFE AF: 0.611

Gnomad OTH AF: 0.687

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

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.684 AC: 73856 AN: 107916 Hom.: 18820 Cov.: 21 AF XY: 0.674 AC XY: 20443 AN XY: 30328

Gnomad4 AFR AF: 0.840

Gnomad4 AMR AF: 0.676

Gnomad4 ASJ AF: 0.562

Gnomad4 EAS AF: 0.771

Gnomad4 SAS AF: 0.583

Gnomad4 FIN AF: 0.616

Gnomad4 NFE AF: 0.611

Gnomad4 OTH AF: 0.692

Alfa AF: 0.429 Hom.: 1638

Bravo AF: 0.698

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.6
DANN	Benign	0.86

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: rs11094201; hg19: chrX-70441731;