Variant 1-147907897-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.210

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 -20 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_multiple_submitters_no_conflicts, 2 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 GnomAd4 at 83 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GJA8	NM_005267.5 linkuse as main transcript	c.-11-48G>T		intron_variant		ENST00000369235.2	NP_005258.2
GJA8	XM_011509417.3 linkuse as main transcript	c.-59G>T		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 linkuse as main transcript	c.-11-48G>T		intron_variant			NM_005267.5	ENSP00000358238	P1

Frequencies

GnomAD3 genomes

AF:

0.0291

AC:

4425

AN:

152082

Hom.:

Cov.:

show subpopulations

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

show subpopulations

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.:

Cov.:

AF XY:

0.0289

AC XY:

2153

AN XY:

74392

show subpopulations

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.:

Bravo

AF:

0.0250

Asia WGS

AF:

0.00375

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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	Oct 09, 2018	- -

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

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