chrX-71223930-C-A

Variant names:

• chrX-71223930-C-A
• rs116840819
• NM_000166.6:c.223C>A

Variant summary

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

The NM_000166.6(GJB1):​c.223C>A​(p.Arg75Arg) variant causes a synonymous change. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 23)
• Consequence: GJB1 NM_000166.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.92
• Publications: 41 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, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Orphanet
• 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=-0.35).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000166.6. 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_000166.6	MANE Select	c.223C>A	p.Arg75Arg	synonymous	Exon 2 of 2	NP_000157.1	P08034
	GJB1	NM_001097642.3		c.223C>A	p.Arg75Arg	synonymous	Exon 2 of 2	NP_001091111.1	P08034
	GJB1	NM_001440770.1		c.223C>A	p.Arg75Arg	synonymous	Exon 3 of 3	NP_001427699.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GJB1	ENST00000361726.7	TSL:1 MANE Select	c.223C>A	p.Arg75Arg	synonymous	Exon 2 of 2	ENSP00000354900.6	P08034
	GJB1	ENST00000374029.2	TSL:5	c.223C>A	p.Arg75Arg	synonymous	Exon 2 of 2	ENSP00000363141.1	P08034
	GJB1	ENST00000447581.2	TSL:5	c.223C>A	p.Arg75Arg	synonymous	Exon 3 of 3	ENSP00000407223.2	P08034

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	11
DANN	Benign	0.58
PhyloP100		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs116840819; hg19: chrX-70443780;