13-20224101-A-G

Position:

• chr13-20224101-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001110219.3(GJB6):​c.-15-606T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.565 in 151,966 control chromosomes in the GnomAD database, including 24,470 homozygotes. 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 0.56 (24470 hom., cov: 32)
• Consequence: GJB6 NM_001110219.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.463

Genes affected

GJB6 (HGNC:4288): (gap junction protein beta 6) Gap junctions allow the transport of ions and metabolites between the cytoplasm of adjacent cells. They are formed by two hemichannels, made up of six connexin proteins assembled in groups. Each connexin protein has four transmembrane segments, two extracellular loops, a cytoplasmic loop formed between the two inner transmembrane segments, and the N- and C-terminus both being in the cytoplasm. The specificity of the gap junction is determined by which connexin proteins comprise the hemichannel. In the past, connexin protein names were based on their molecular weight, however the new nomenclature uses sequential numbers based on which form (alpha or beta) of the gap junction is present. This gene encodes one of the connexin proteins. Mutations in this gene have been found in some forms of deafness and in some families with hidrotic ectodermal dysplasia. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.659 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GJB6	NM_001110219.3	c.-15-606T>C		intron_variant		ENST00000647029.1	NP_001103689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GJB6	ENST00000647029.1	c.-15-606T>C		intron_variant			NM_001110219.3	ENSP00000493834.1

Frequencies

GnomAD3 genomes AF: 0.564 AC: 85718 AN: 151848 Hom.: 24442 Cov.: 32

Gnomad AFR AF: 0.573

Gnomad AMI AF: 0.523

Gnomad AMR AF: 0.670

Gnomad ASJ AF: 0.582

Gnomad EAS AF: 0.663

Gnomad SAS AF: 0.616

Gnomad FIN AF: 0.474

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.539

Gnomad OTH AF: 0.556

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

GnomAD4 genome AF: 0.565 AC: 85806 AN: 151966 Hom.: 24470 Cov.: 32 AF XY: 0.564 AC XY: 41910 AN XY: 74260

Gnomad4 AFR AF: 0.573

Gnomad4 AMR AF: 0.670

Gnomad4 ASJ AF: 0.582

Gnomad4 EAS AF: 0.663

Gnomad4 SAS AF: 0.616

Gnomad4 FIN AF: 0.474

Gnomad4 NFE AF: 0.539

Gnomad4 OTH AF: 0.556

Alfa AF: 0.548 Hom.: 18797

Bravo AF: 0.583

Asia WGS AF: 0.650 AC: 2257 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.6
DANN	Benign	0.50

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: rs877098; hg19: chr13-20798240;