Genetic Variant NM_145740.5:c.546+102G>A (chr6-52792754-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_145740.5(GSTA1):c.546+102G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.599 in 1,609,306 control chromosomes in the GnomAD database, including 293,306 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 0.64 ( 31321 hom., cov: 31)

Exomes 𝑓: 0.60 ( 261985 hom. )

Consequence

GSTA1
NM_145740.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.273

Variant links:

Genes affected

GSTA1 (HGNC:4626): (glutathione S-transferase alpha 1) This gene encodes a member of a family of enzymes that function to add glutathione to target electrophilic compounds, including carcinogens, therapeutic drugs, environmental toxins, and products of oxidative stress. This action is an important step in detoxification of these compounds. This subfamily of enzymes has a particular role in protecting cells from reactive oxygen species and the products of peroxidation. Polymorphisms in this gene influence the ability of individuals to metabolize different drugs. This gene is located in a cluster of similar genes and pseudogenes on chromosome 6. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

GSTA1 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=-0.88).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.852 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSTA1	NM_145740.5 link	c.546+102G>A		intron_variant	Intron 6 of 6	ENST00000334575.6	NP_665683.1	P08263A0A140VJK4
GSTA1	XM_005249034.5 link	c.648G>A	p.Gln216Gln	synonymous_variant	Exon 6 of 6		XP_005249091.1	B7Z1F9
GSTA1	NM_001319059.2 link	c.267+102G>A		intron_variant	Intron 5 of 5		NP_001305988.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSTA1	ENST00000334575.6 link	c.546+102G>A		intron_variant	Intron 6 of 6	1	NM_145740.5	ENSP00000335620.5		P08263
GSTA1	ENST00000493331.5 link	n.443+102G>A		intron_variant	Intron 4 of 4	2

Frequencies

GnomAD3 genomes

AF:

0.635

AC:

96508

AN:

151864

Hom.:

31300

Cov.:

show subpopulations

Gnomad AFR

AF:

0.702

Gnomad AMI

AF:

0.658

Gnomad AMR

AF:

0.701

Gnomad ASJ

AF:

0.568

Gnomad EAS

AF:

0.874

Gnomad SAS

AF:

0.661

Gnomad FIN

AF:

0.564

Gnomad MID

AF:

0.599

Gnomad NFE

AF:

0.575

Gnomad OTH

AF:

0.630

GnomAD3 exomes

AF:

0.641

AC:

159566

AN:

249056

Hom.:

52543

AF XY:

0.631

AC XY:

85152

AN XY:

134936

show subpopulations

Gnomad AFR exome

AF:

0.697

Gnomad AMR exome

AF:

0.773

Gnomad ASJ exome

AF:

0.547

Gnomad EAS exome

AF:

0.877

Gnomad SAS exome

AF:

0.652

Gnomad FIN exome

AF:

0.562

Gnomad NFE exome

AF:

0.575

Gnomad OTH exome

AF:

0.619

GnomAD4 exome

AF:

0.596

AC:

868149

AN:

1457324

Hom.:

261985

Cov.:

AF XY:

0.596

AC XY:

432038

AN XY:

724968

show subpopulations

Gnomad4 AFR exome

AF:

0.700

Gnomad4 AMR exome

AF:

0.762

Gnomad4 ASJ exome

AF:

0.544

Gnomad4 EAS exome

AF:

0.874

Gnomad4 SAS exome

AF:

0.649

Gnomad4 FIN exome

AF:

0.563

Gnomad4 NFE exome

AF:

0.574

Gnomad4 OTH exome

AF:

0.613

GnomAD4 genome

AF:

0.635

AC:

96577

AN:

151982

Hom.:

31321

Cov.:

AF XY:

0.639

AC XY:

47449

AN XY:

74292

show subpopulations

Gnomad4 AFR

AF:

0.701

Gnomad4 AMR

AF:

0.702

Gnomad4 ASJ

AF:

0.568

Gnomad4 EAS

AF:

0.873

Gnomad4 SAS

AF:

0.660

Gnomad4 FIN

AF:

0.564

Gnomad4 NFE

AF:

0.575

Gnomad4 OTH

AF:

0.633

Alfa

AF:

0.580

Hom.:

33629

Bravo

AF:

0.649

Asia WGS

AF:

0.742

AC:

2579

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

8.0

DANN

Benign

0.55

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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