1-147907897-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_005267.5(GJA8):c.-11-48G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0363 in 1,301,272 control chromosomes in the GnomAD database, including 1,099 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.029 (83 hom., cov: 32)
  • Exomes 𝑓: 0.037 (1016 hom.)
• Consequence: GJA8 NM_005267.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.210

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 1-147907897-G-T is Benign according to our data. Variant chr1-147907897-G-T is described in ClinVar as [Benign]. Clinvar id is 1273241.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0291 (4425/152200) while in subpopulation NFE AF= 0.0457 (3111/68010). AF 95% confidence interval is 0.0444. There are 83 homozygotes in gnomad4. There are 2153 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 83 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GJA8	NM_005267.5	c.-11-48G>T		intron_variant		ENST00000369235.2
GJA8	XM_011509417.3	c.-59G>T		5_prime_UTR_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GJA8	ENST00000369235.2	c.-11-48G>T		intron_variant			NM_005267.5	P1

Frequencies

GnomAD3 genomes AF: 0.0291 AC: 4425 AN: 152082 Hom.: 83 Cov.: 32

Gnomad AFR AF: 0.00748

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0216

Gnomad ASJ AF: 0.0153

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00602

Gnomad FIN AF: 0.0512

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0457

Gnomad OTH AF: 0.0234

GnomAD4 exome AF: 0.0373 AC: 42864 AN: 1149072 Hom.: 1016 AF XY: 0.0364 AC XY: 21330 AN XY: 585972

Gnomad4 AFR exome AF: 0.00599

Gnomad4 AMR exome AF: 0.0138

Gnomad4 ASJ exome AF: 0.0189

Gnomad4 EAS exome AF: 0.0000522

Gnomad4 SAS exome AF: 0.00596

Gnomad4 FIN exome AF: 0.0522

Gnomad4 NFE exome AF: 0.0445

Gnomad4 OTH exome AF: 0.0325

GnomAD4 genome AF: 0.0291 AC: 4425 AN: 152200 Hom.: 83 Cov.: 32 AF XY: 0.0289 AC XY: 2153 AN XY: 74392

Gnomad4 AFR AF: 0.00746

Gnomad4 AMR AF: 0.0216

Gnomad4 ASJ AF: 0.0153

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00603

Gnomad4 FIN AF: 0.0512

Gnomad4 NFE AF: 0.0457

Gnomad4 OTH AF: 0.0232

Alfa AF: 0.0405 Hom.: 22

Bravo AF: 0.0250

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 09, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	1.7
Dann	Benign	0.72

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs115981722; hg19: chr1-147380024;