chrX-71223112-T-G

Variant names:

• chrX-71223112-T-G
• ENST00000870749.1:c.-596T>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001097642.3(GJB1):​c.-16-580T>G variant causes a intron change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: GJB1 NM_001097642.3 intron
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.67
• Publications: 0 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: PanelApp Australia, Orphanet, ClinGen, Labcorp Genetics (formerly Invitae)
• X-linked progressive cerebellar ataxia

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001097642.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GJB1	NM_001097642.3		c.-16-580T>G		intron	N/A	NP_001091111.1	P08034
	GJB1	NM_001440770.1		c.-17+346T>G		intron	N/A	NP_001427699.1
	GJB1	NM_000166.6	MANE Select	c.-240T>G		upstream_gene	N/A	NP_000157.1	P08034

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GJB1	ENST00000870749.1		c.-596T>G		5_prime_UTR	Exon 2 of 2	ENSP00000540808.1
	GJB1	ENST00000870756.1		c.-596T>G		5_prime_UTR	Exon 2 of 2	ENSP00000540815.1
	GJB1	ENST00000374029.2	TSL:5	c.-16-580T>G		intron	N/A	ENSP00000363141.1	P08034

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 17565 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 3815

African (AFR) AF: 0.00 AC: 0 AN: 545

American (AMR) AF: 0.00 AC: 0 AN: 2141

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 246

East Asian (EAS) AF: 0.00 AC: 0 AN: 1247

South Asian (SAS) AF: 0.00 AC: 0 AN: 1326

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 542

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 29

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 10592

Other (OTH) AF: 0.00 AC: 0 AN: 897

GnomAD4 genome Cov.: 23

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	22
DANN	Benign	0.87
PhyloP100		6.7
PromoterAI		-0.0022	Neutral

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

hg19: chrX-70442962;