Genetic Variant GSTA4:c.88-2902G>A (chr6-52990310-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001512.4(GSTA4):c.88-2902G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0163 in 152,284 control chromosomes in the GnomAD database, including 41 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 0.016 ( 41 hom., cov: 32)

Consequence

GSTA4
NM_001512.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.129

Publications

1 publications found

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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0505 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
GSTA4	NM_001512.4 link	c.88-2902G>A	intron_variant	Intron 2 of 6	ENST00000370963.9	NP_001503.1	O15217-1A0A024RD58
GSTA4	XM_005249035.5 link	c.88-2902G>A	intron_variant	Intron 2 of 6		XP_005249092.1	O15217-1A0A024RD58
GSTA4	XM_011514534.4 link	c.28+3847G>A	intron_variant	Intron 2 of 5		XP_011512836.1
GSTA4	XM_011514535.4 link	c.28+3847G>A	intron_variant	Intron 2 of 5		XP_011512837.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSTA4	ENST00000370963.9 link	c.88-2902G>A		intron_variant	Intron 2 of 6	1	NM_001512.4	ENSP00000360002.4		O15217-1

Frequencies

GnomAD3 genomes

AF:

0.0163

AC:

2487

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00280

Gnomad AMI

AF:

0.0121

Gnomad AMR

AF:

0.00792

Gnomad ASJ

AF:

0.0407

Gnomad EAS

AF:

0.0559

Gnomad SAS

AF:

0.0224

Gnomad FIN

AF:

0.0627

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0144

Gnomad OTH

AF:

0.0201

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

GnomAD4 genome

AF:

0.0163

AC:

2483

AN:

152284

Hom.:

Cov.:

AF XY:

0.0184

AC XY:

1368

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.00279

AC:

116

AN:

41574

American (AMR)

AF:

0.00791

AC:

121

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0407

AC:

141

AN:

3468

East Asian (EAS)

AF:

0.0558

AC:

289

AN:

5180

South Asian (SAS)

AF:

0.0224

AC:

108

AN:

4818

European-Finnish (FIN)

AF:

0.0627

AC:

665

AN:

10608

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0144

AC:

979

AN:

68014

Other (OTH)

AF:

0.0198

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

122

244

365

487

609

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

160

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00968

Hom.:

Bravo

AF:

0.0124

Asia WGS

AF:

0.0280

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

1.6

(source)

DANN

Benign

0.43

PhyloP100

-0.13

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over