1-147907814-A-G

Position:

• chr1-147907814-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005267.5(GJA8):​c.-11-131A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0479 in 734,090 control chromosomes in the GnomAD database, including 1,371 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.056 (337 hom., cov: 32)
  • Exomes 𝑓: 0.046 (1034 hom.)
• Consequence: GJA8 NM_005267.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0110

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 1-147907814-A-G is Benign according to our data. Variant chr1-147907814-A-G is described in ClinVar as [Benign]. Clinvar id is 1267692.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GJA8	NM_005267.5	c.-11-131A>G		intron_variant		ENST00000369235.2	NP_005258.2
GJA8	XM_011509417.3	c.-142A>G		5_prime_UTR_variant	1/2		XP_011507719.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GJA8	ENST00000369235.2	c.-11-131A>G		intron_variant			NM_005267.5	ENSP00000358238	P1

Frequencies

GnomAD3 genomes AF: 0.0558 AC: 8488 AN: 152088 Hom.: 338 Cov.: 32

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0357

Gnomad ASJ AF: 0.0193

Gnomad EAS AF: 0.0824

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.0489

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0291

Gnomad OTH AF: 0.0416

GnomAD4 exome AF: 0.0459 AC: 26690 AN: 581884 Hom.: 1034 AF XY: 0.0498 AC XY: 15742 AN XY: 316030

Gnomad4 AFR exome AF: 0.101

Gnomad4 AMR exome AF: 0.0279

Gnomad4 ASJ exome AF: 0.0194

Gnomad4 EAS exome AF: 0.0781

Gnomad4 SAS exome AF: 0.121

Gnomad4 FIN exome AF: 0.0489

Gnomad4 NFE exome AF: 0.0291

Gnomad4 OTH exome AF: 0.0432

GnomAD4 genome AF: 0.0559 AC: 8502 AN: 152206 Hom.: 337 Cov.: 32 AF XY: 0.0578 AC XY: 4300 AN XY: 74424

Gnomad4 AFR AF: 0.102

Gnomad4 AMR AF: 0.0357

Gnomad4 ASJ AF: 0.0193

Gnomad4 EAS AF: 0.0822

Gnomad4 SAS AF: 0.132

Gnomad4 FIN AF: 0.0489

Gnomad4 NFE AF: 0.0291

Gnomad4 OTH AF: 0.0440

Alfa AF: 0.0414 Hom.: 49

Bravo AF: 0.0536

Asia WGS AF: 0.135 AC: 467 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 31, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.4
DANN	Benign	0.48

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17160783; hg19: chr1-147379941;