Variant 1-147908759-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_005267.5(GJA8):c.804C>T(p.Leu268=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0423 in 1,614,040 control chromosomes in the GnomAD database, including 1,643 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.047 ( 206 hom., cov: 32)

Exomes 𝑓: 0.042 ( 1437 hom. )

Consequence

GJA8
NM_005267.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.442

Variant links:

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]

GJA8 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant 1-147908759-C-T is Benign according to our data. Variant chr1-147908759-C-T is described in ClinVar as [Benign]. Clinvar id is 259707.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-147908759-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=0.442 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0689 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GJA8	NM_005267.5 linkuse as main transcript	c.804C>T	p.Leu268=	synonymous_variant	2/2	ENST00000369235.2	NP_005258.2
GJA8	XM_011509417.3 linkuse as main transcript	c.804C>T	p.Leu268=	synonymous_variant	1/2		XP_011507719.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GJA8	ENST00000369235.2 linkuse as main transcript	c.804C>T	p.Leu268=	synonymous_variant	2/2		NM_005267.5	ENSP00000358238	P1

Frequencies

GnomAD3 genomes

AF:

0.0471

AC:

7171

AN:

152136

Hom.:

204

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0709

Gnomad AMI

AF:

0.00330

Gnomad AMR

AF:

0.0245

Gnomad ASJ

AF:

0.0496

Gnomad EAS

AF:

0.0491

Gnomad SAS

AF:

0.0660

Gnomad FIN

AF:

0.0382

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0385

Gnomad OTH

AF:

0.0378

GnomAD3 exomes

AF:

0.0403

AC:

10130

AN:

251406

Hom.:

272

AF XY:

0.0410

AC XY:

5568

AN XY:

135910

show subpopulations

Gnomad AFR exome

AF:

0.0734

Gnomad AMR exome

AF:

0.0154

Gnomad ASJ exome

AF:

0.0509

Gnomad EAS exome

AF:

0.0344

Gnomad SAS exome

AF:

0.0685

Gnomad FIN exome

AF:

0.0358

Gnomad NFE exome

AF:

0.0362

Gnomad OTH exome

AF:

0.0438

GnomAD4 exome

AF:

0.0418

AC:

61056

AN:

1461786

Hom.:

1437

Cov.:

AF XY:

0.0422

AC XY:

30699

AN XY:

727202

show subpopulations

Gnomad4 AFR exome

AF:

0.0758

Gnomad4 AMR exome

AF:

0.0165

Gnomad4 ASJ exome

AF:

0.0477

Gnomad4 EAS exome

AF:

0.0450

Gnomad4 SAS exome

AF:

0.0680

Gnomad4 FIN exome

AF:

0.0377

Gnomad4 NFE exome

AF:

0.0395

Gnomad4 OTH exome

AF:

0.0450

GnomAD4 genome

AF:

0.0472

AC:

7181

AN:

152254

Hom.:

206

Cov.:

AF XY:

0.0479

AC XY:

3566

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.0710

Gnomad4 AMR

AF:

0.0245

Gnomad4 ASJ

AF:

0.0496

Gnomad4 EAS

AF:

0.0490

Gnomad4 SAS

AF:

0.0663

Gnomad4 FIN

AF:

0.0382

Gnomad4 NFE

AF:

0.0385

Gnomad4 OTH

AF:

0.0369

Alfa

AF:

0.0430

Hom.:

Bravo

AF:

0.0453

Asia WGS

AF:

0.0950

AC:

329

AN:

3478

EpiCase

AF:

0.0354

EpiControl

AF:

0.0343

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 31, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Cataract 1 multiple types

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 16, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Zonular Pulverulent Cataract

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

2.6

DANN

Benign

0.70

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over