1-147907615-A-G

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.-11-330A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0344 in 152,294 control chromosomes in the GnomAD database, including 103 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.034 (103 hom., cov: 32)
• Consequence: GJA8 NM_005267.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.96

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=-0.82).
• BP6: Variant 1-147907615-A-G is Benign according to our data. Variant chr1-147907615-A-G is described in ClinVar as [Benign]. Clinvar id is 1273012.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0344 (5243/152294) while in subpopulation NFE AF= 0.0459 (3119/68026). AF 95% confidence interval is 0.0445. There are 103 homozygotes in gnomad4. There are 2555 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 103 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GJA8	NM_005267.5	c.-11-330A>G		intron_variant		ENST00000369235.2
GJA8	XM_011509417.3	c.-341A>G		5_prime_UTR_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GJA8	ENST00000369235.2	c.-11-330A>G		intron_variant			NM_005267.5	P1

Frequencies

GnomAD3 genomes AF: 0.0344 AC: 5241 AN: 152176 Hom.: 103 Cov.: 32

Gnomad AFR AF: 0.0259

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0236

Gnomad ASJ AF: 0.0153

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00622

Gnomad FIN AF: 0.0513

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0458

Gnomad OTH AF: 0.0268

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

GnomAD4 genome AF: 0.0344 AC: 5243 AN: 152294 Hom.: 103 Cov.: 32 AF XY: 0.0343 AC XY: 2555 AN XY: 74454

Gnomad4 AFR AF: 0.0259

Gnomad4 AMR AF: 0.0235

Gnomad4 ASJ AF: 0.0153

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00622

Gnomad4 FIN AF: 0.0513

Gnomad4 NFE AF: 0.0459

Gnomad4 OTH AF: 0.0265

Alfa AF: 0.0434 Hom.: 22

Bravo AF: 0.0315

Asia WGS AF: 0.00433 AC: 15 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 01, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	10
Dann	Benign	0.68

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs78669708; hg19: chr1-147379742;