rs5980747

Variant names:

• chrX-71221540-G-C
• rs5980747
• NM_001097642.3:c.-16-2152G>C

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Likely benign. The variant received -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
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• Charcot-Marie-Tooth disease X-linked dominant 1

  Inheritance: XL Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, PanelApp Australia, ClinGen, Labcorp Genetics (formerly Invitae)
• X-linked progressive cerebellar ataxia

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GJB1	NM_001097642.3	c.-16-2152G>C		intron_variant	Intron 1 of 1		NP_001091111.1
GJB1	NM_001440770.1	c.-199-1044G>C		intron_variant	Intron 1 of 2		NP_001427699.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GJB1	ENST00000374029.2	c.-16-2152G>C		intron_variant	Intron 1 of 1	5		ENSP00000363141.1
GJB1	ENST00000447581.2	c.-199-1044G>C		intron_variant	Intron 1 of 2	5		ENSP00000407223.2
GJB1	ENST00000645009.2	c.-16-2152G>C		intron_variant	Intron 1 of 1			ENSP00000494142.2

Frequencies

GnomAD3 genomes AF: 0.698 AC: 75728 AN: 108565 Hom.: 20037 Cov.: 21

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

African (AFR) AF: 0.930 AC: 27752 AN: 29833

American (AMR) AF: 0.682 AC: 6853 AN: 10044

Ashkenazi Jewish (ASJ) AF: 0.583 AC: 1531 AN: 2627

East Asian (EAS) AF: 0.770 AC: 2629 AN: 3414

South Asian (SAS) AF: 0.591 AC: 1484 AN: 2512

European-Finnish (FIN) AF: 0.594 AC: 3255 AN: 5482

Middle Eastern (MID) AF: 0.586 AC: 123 AN: 210

European-Non Finnish (NFE) AF: 0.587 AC: 30742 AN: 52378

Other (OTH) AF: 0.693 AC: 1007 AN: 1453

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
PhyloP100		0.35
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs5980747; hg19: chrX-70441390;