Genetic Variant GSTA4:c.*137C>A (chr6-52978333-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001512.4(GSTA4):c.*137C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.601 in 800,630 control chromosomes in the GnomAD database, including 145,864 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.57 ( 24965 hom., cov: 31)

Exomes 𝑓: 0.61 ( 120899 hom. )

Consequence

GSTA4
NM_001512.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.62

Variant links:

Genes affected

GSTA4 (HGNC:4629): (glutathione S-transferase alpha 4) Cytosolic and membrane-bound forms of glutathione S-transferase are encoded by two distinct supergene families. These enzymes are involved in cellular defense against toxic, carcinogenic, and pharmacologically active electrophilic compounds. At present, eight distinct classes of the soluble cytoplasmic mammalian glutathione S-transferases have been identified: alpha, kappa, mu, omega, pi, sigma, theta and zeta. This gene encodes a glutathione S-tranferase belonging to the alpha class. The alpha class genes, which are located in a cluster on chromosome 6, are highly related and encode enzymes with glutathione peroxidase activity that function in the detoxification of lipid peroxidation products. Reactive electrophiles produced by oxidative metabolism have been linked to a number of degenerative diseases including Parkinson's disease, Alzheimer's disease, cataract formation, and atherosclerosis. [provided by RefSeq, Jul 2008]

GSTA4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.721 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
GSTA4	NM_001512.4 link	c.*137C>A	3_prime_UTR_variant	Exon 7 of 7	ENST00000370963.9	NP_001503.1	O15217-1A0A024RD58
GSTA4	XM_005249035.5 link	c.*137C>A	3_prime_UTR_variant	Exon 7 of 7		XP_005249092.1	O15217-1A0A024RD58
GSTA4	XM_011514534.4 link	c.*137C>A	3_prime_UTR_variant	Exon 6 of 6		XP_011512836.1
GSTA4	XM_011514535.4 link	c.*137C>A	3_prime_UTR_variant	Exon 6 of 6		XP_011512837.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSTA4	ENST00000370963 link	c.*137C>A		3_prime_UTR_variant	Exon 7 of 7	1	NM_001512.4	ENSP00000360002.4		O15217-1

Frequencies

GnomAD3 genomes

AF:

0.571

AC:

86637

AN:

151832

Hom.:

24960

Cov.:

show subpopulations

Gnomad AFR

AF:

0.520

Gnomad AMI

AF:

0.525

Gnomad AMR

AF:

0.513

Gnomad ASJ

AF:

0.595

Gnomad EAS

AF:

0.741

Gnomad SAS

AF:

0.647

Gnomad FIN

AF:

0.531

Gnomad MID

AF:

0.650

Gnomad NFE

AF:

0.601

Gnomad OTH

AF:

0.571

GnomAD4 exome

AF:

0.609

AC:

394723

AN:

648678

Hom.:

120899

Cov.:

AF XY:

0.610

AC XY:

210271

AN XY:

344540

show subpopulations

Gnomad4 AFR exome

AF:

0.516

Gnomad4 AMR exome

AF:

0.498

Gnomad4 ASJ exome

AF:

0.599

Gnomad4 EAS exome

AF:

0.775

Gnomad4 SAS exome

AF:

0.640

Gnomad4 FIN exome

AF:

0.539

Gnomad4 NFE exome

AF:

0.609

Gnomad4 OTH exome

AF:

0.598

GnomAD4 genome

AF:

0.570

AC:

86661

AN:

151952

Hom.:

24965

Cov.:

AF XY:

0.568

AC XY:

42184

AN XY:

74272

show subpopulations

Gnomad4 AFR

AF:

0.519

Gnomad4 AMR

AF:

0.513

Gnomad4 ASJ

AF:

0.595

Gnomad4 EAS

AF:

0.741

Gnomad4 SAS

AF:

0.648

Gnomad4 FIN

AF:

0.531

Gnomad4 NFE

AF:

0.601

Gnomad4 OTH

AF:

0.574

Alfa

AF:

0.599

Hom.:

54496

Bravo

AF:

0.567

Asia WGS

AF:

0.658

AC:

2287

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.13

DANN

Benign

0.45

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over