dbSNP rs405729: GSTA4:c.*487A>G (chr6-52977983-T-C) – 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.*487A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.513 in 152,888 control chromosomes in the GnomAD database, including 20,522 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 0.51 ( 20434 hom., cov: 33)

Exomes 𝑓: 0.46 ( 88 hom. )

Consequence

GSTA4
NM_001512.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.335

Publications

13 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:

Genome browser will be placed here

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 = 0.722 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
GSTA4	NM_001512.4 link	c.*487A>G	3_prime_UTR_variant	Exon 7 of 7	ENST00000370963.9	NP_001503.1	O15217-1A0A024RD58
GSTA4	XM_005249035.5 link	c.*487A>G	3_prime_UTR_variant	Exon 7 of 7		XP_005249092.1	O15217-1A0A024RD58
GSTA4	XM_011514534.4 link	c.*487A>G	3_prime_UTR_variant	Exon 6 of 6		XP_011512836.1
GSTA4	XM_011514535.4 link	c.*487A>G	3_prime_UTR_variant	Exon 6 of 6		XP_011512837.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
GSTA4	ENST00000370963.9 link	c.*487A>G	3_prime_UTR_variant	Exon 7 of 7	1	NM_001512.4	ENSP00000360002.4	O15217-1
GSTA4	ENST00000477599.5 link	n.1097A>G	non_coding_transcript_exon_variant	Exon 6 of 6	3
GSTA4	ENST00000486559.5 link	n.1663A>G	non_coding_transcript_exon_variant	Exon 5 of 5	2

Frequencies

GnomAD3 genomes

AF:

0.514

AC:

78108

AN:

151998

Hom.:

20430

Cov.:

show subpopulations

Gnomad AFR

AF:

0.472

Gnomad AMI

AF:

0.497

Gnomad AMR

AF:

0.461

Gnomad ASJ

AF:

0.523

Gnomad EAS

AF:

0.742

Gnomad SAS

AF:

0.613

Gnomad FIN

AF:

0.464

Gnomad MID

AF:

0.585

Gnomad NFE

AF:

0.534

Gnomad OTH

AF:

0.518

GnomAD4 exome

AF:

0.460

AC:

355

AN:

772

Hom.:

Cov.:

AF XY:

0.488

AC XY:

207

AN XY:

424

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.583

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AF:

0.929

AC:

AN:

South Asian (SAS)

AF:

0.548

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AF:

0.250

AC:

AN:

European-Non Finnish (NFE)

AF:

0.450

AC:

272

AN:

604

Other (OTH)

AF:

0.429

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.514

AC:

78133

AN:

152116

Hom.:

20434

Cov.:

AF XY:

0.513

AC XY:

38166

AN XY:

74358

show subpopulations

African (AFR)

AF:

0.471

AC:

19564

AN:

41510

American (AMR)

AF:

0.461

AC:

7045

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.523

AC:

1813

AN:

3468

East Asian (EAS)

AF:

0.742

AC:

3834

AN:

5170

South Asian (SAS)

AF:

0.615

AC:

2962

AN:

4820

European-Finnish (FIN)

AF:

0.464

AC:

4904

AN:

10566

Middle Eastern (MID)

AF:

0.595

AC:

175

AN:

294

European-Non Finnish (NFE)

AF:

0.534

AC:

36282

AN:

67978

Other (OTH)

AF:

0.521

AC:

1102

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1960

3919

5879

7838

9798

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

712

1424

2136

2848

3560

<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:

0.534

Hom.:

64514

Bravo

AF:

0.511

Asia WGS

AF:

0.643

AC:

2237

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

4.3

(source)

DANN

Benign

0.50

PhyloP100

0.34

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over