Genetic Variant NM_001512.4:c.*137C>A (chr6-52978333-G-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.*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

Publications

20 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=-0.97).

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	ENST00000370963.9 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

African (AFR)

AF:

0.516

AC:

7289

AN:

14118

American (AMR)

AF:

0.498

AC:

10758

AN:

21582

Ashkenazi Jewish (ASJ)

AF:

0.599

AC:

10891

AN:

18196

East Asian (EAS)

AF:

0.775

AC:

24243

AN:

31298

South Asian (SAS)

AF:

0.640

AC:

35133

AN:

54882

European-Finnish (FIN)

AF:

0.539

AC:

24218

AN:

44908

Middle Eastern (MID)

AF:

0.632

AC:

2557

AN:

4046

European-Non Finnish (NFE)

AF:

0.609

AC:

260124

AN:

427028

Other (OTH)

AF:

0.598

AC:

19510

AN:

32620

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

7376

14752

22127

29503

36879

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3590

7180

10770

14360

17950

<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:

0.570

AC:

86661

AN:

151952

Hom.:

24965

Cov.:

AF XY:

0.568

AC XY:

42184

AN XY:

74272

show subpopulations

African (AFR)

AF:

0.519

AC:

21496

AN:

41412

American (AMR)

AF:

0.513

AC:

7842

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.595

AC:

2065

AN:

3470

East Asian (EAS)

AF:

0.741

AC:

3827

AN:

5164

South Asian (SAS)

AF:

0.648

AC:

3127

AN:

4822

European-Finnish (FIN)

AF:

0.531

AC:

5591

AN:

10534

Middle Eastern (MID)

AF:

0.650

AC:

191

AN:

294

European-Non Finnish (NFE)

AF:

0.601

AC:

40840

AN:

67962

Other (OTH)

AF:

0.574

AC:

1204

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1952

3904

5856

7808

9760

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

752

1504

2256

3008

3760

<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:

0.596

Hom.:

76154

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

(source)

DANN

Benign

0.45

PhyloP100

-3.6

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