rs5980747

Positions:

• chrX-71221540-G-C
• chrX-71221540-G-T

Variant summary

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

The NM_001097642.3(GJB1):​c.-16-2152G>C 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 0.70 (20046 hom., 21300 hem., cov: 21)
  • Failed GnomAD Quality Control
• Consequence: GJB1 NM_001097642.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.353

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=-0.97).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GJB1	NM_001097642.3	c.-16-2152G>C		intron_variant			NP_001091111.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GJB1	ENST00000374029.2	c.-16-2152G>C		intron_variant		5		ENSP00000363141.1
GJB1	ENST00000447581.2	c.-199-1044G>C		intron_variant		5		ENSP00000407223.2
GJB1	ENST00000645009.2	c.-16-2152G>C		intron_variant				ENSP00000494142.2

Frequencies

GnomAD3 genomes AF: 0.698 AC: 75728 AN: 108565 Hom.: 20037 Cov.: 21 AF XY: 0.687 AC XY: 21244 AN XY: 30905

Gnomad AFR AF: 0.930

Gnomad AMI AF: 0.628

Gnomad AMR AF: 0.682

Gnomad ASJ AF: 0.583

Gnomad EAS AF: 0.770

Gnomad SAS AF: 0.593

Gnomad FIN AF: 0.594

Gnomad MID AF: 0.578

Gnomad NFE AF: 0.587

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: 0.698 AC: 75791 AN: 108614 Hom.: 20046 Cov.: 21 AF XY: 0.688 AC XY: 21300 AN XY: 30964

Gnomad4 AFR AF: 0.930

Gnomad4 AMR AF: 0.682

Gnomad4 ASJ AF: 0.583

Gnomad4 EAS AF: 0.770

Gnomad4 SAS AF: 0.591

Gnomad4 FIN AF: 0.594

Gnomad4 NFE AF: 0.587

Gnomad4 OTH AF: 0.693

Alfa AF: 0.638 Hom.: 4768

Bravo AF: 0.715

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	5.7
DANN	Benign	0.43

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: rs5980747; hg19: chrX-70441390;