Genetic Variant NM_001512.4:c.547-795C>T (chr6-52979387-G-A) – 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.547-795C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.926 in 152,322 control chromosomes in the GnomAD database, including 65,331 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 0.93 ( 65331 hom., cov: 33)

Consequence

GSTA4
NM_001512.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.821

Publications

3 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=-0.94).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001512.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSTA4	NM_001512.4	MANE Select	c.547-795C>T		intron	N/A	NP_001503.1	O15217-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GSTA4	ENST00000370963.9	TSL:1 MANE Select	c.547-795C>T	intron	N/A	ENSP00000360002.4	O15217-1
GSTA4	ENST00000370959.1	TSL:5	c.547-795C>T	intron	N/A	ENSP00000359998.1	O15217-1
GSTA4	ENST00000887782.1		c.547-795C>T	intron	N/A	ENSP00000557841.1

Frequencies

GnomAD3 genomes

AF:

0.926

AC:

140902

AN:

152204

Hom.:

65276

Cov.:

show subpopulations

Gnomad AFR

AF:

0.931

Gnomad AMI

AF:

0.962

Gnomad AMR

AF:

0.939

Gnomad ASJ

AF:

0.954

Gnomad EAS

AF:

0.999

Gnomad SAS

AF:

0.985

Gnomad FIN

AF:

0.915

Gnomad MID

AF:

0.953

Gnomad NFE

AF:

0.909

Gnomad OTH

AF:

0.921

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

GnomAD4 genome

AF:

0.926

AC:

141015

AN:

152322

Hom.:

65331

Cov.:

AF XY:

0.927

AC XY:

69067

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.931

AC:

38725

AN:

41576

American (AMR)

AF:

0.939

AC:

14365

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.954

AC:

3312

AN:

3472

East Asian (EAS)

AF:

0.999

AC:

5181

AN:

5186

South Asian (SAS)

AF:

0.985

AC:

4760

AN:

4832

European-Finnish (FIN)

AF:

0.915

AC:

9705

AN:

10612

Middle Eastern (MID)

AF:

0.949

AC:

279

AN:

294

European-Non Finnish (NFE)

AF:

0.909

AC:

61864

AN:

68026

Other (OTH)

AF:

0.922

AC:

1947

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

554

1109

1663

2218

2772

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

912

1824

2736

3648

4560

<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:

0.918

Hom.:

92669

Bravo

AF:

0.927

Asia WGS

AF:

0.985

AC:

3427

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

7.5

(source)

DANN

Benign

0.53

PhyloP100

0.82

Mutation Taster

=100/0

polymorphism (auto)

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over