rs1495960

Positions:

• chr1-147903581-G-T

Variant summary

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

The NM_005267.5(GJA8):​c.-12+720G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.547 in 152,000 control chromosomes in the GnomAD database, including 23,596 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 0.55 (23596 hom., cov: 32)
• Consequence: GJA8 NM_005267.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.31

Genes affected

GJA8 (HGNC:4281): (gap junction protein alpha 8) This gene encodes a transmembrane connexin protein that is necessary for lens growth and maturation of lens fiber cells. The encoded protein is a component of gap junction channels and functions in a calcium and pH-dependent manner. Mutations in this gene have been associated with zonular pulverulent cataracts, nuclear progressive cataracts, and cataract-microcornea syndrome. [provided by RefSeq, Dec 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.689 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GJA8	NM_005267.5	c.-12+720G>T		intron_variant		ENST00000369235.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GJA8	ENST00000369235.2	c.-12+720G>T		intron_variant			NM_005267.5	P1

Frequencies

GnomAD3 genomes AF: 0.547 AC: 83054 AN: 151882 Hom.: 23535 Cov.: 32

Gnomad AFR AF: 0.695

Gnomad AMI AF: 0.384

Gnomad AMR AF: 0.548

Gnomad ASJ AF: 0.461

Gnomad EAS AF: 0.516

Gnomad SAS AF: 0.506

Gnomad FIN AF: 0.436

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.486

Gnomad OTH AF: 0.533

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

GnomAD4 genome AF: 0.547 AC: 83178 AN: 152000 Hom.: 23596 Cov.: 32 AF XY: 0.545 AC XY: 40503 AN XY: 74294

Gnomad4 AFR AF: 0.696

Gnomad4 AMR AF: 0.548

Gnomad4 ASJ AF: 0.461

Gnomad4 EAS AF: 0.515

Gnomad4 SAS AF: 0.506

Gnomad4 FIN AF: 0.436

Gnomad4 NFE AF: 0.486

Gnomad4 OTH AF: 0.539

Alfa AF: 0.513 Hom.: 4828

Bravo AF: 0.559

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.043

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1495960; hg19: chr1-147375707;