Genetic Variant GSTM2:c.361-395A>T (chr1-109670892-A-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_000848.4(GSTM2):c.361-395A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.913 in 175,594 control chromosomes in the GnomAD database, including 73,319 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 0.91 ( 63405 hom., cov: 32)

Exomes 𝑓: 0.92 ( 9914 hom. )

Consequence

GSTM2
NM_000848.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.306

Variant links:

Genes affected

GSTM2 (HGNC:4634): (glutathione S-transferase mu 2) Cytosolic and membrane-bound forms of glutathione S-transferase are encoded by two distinct supergene families. 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-transferase that belongs to the mu class. The mu class of enzymes functions in the detoxification of electrophilic compounds, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress, by conjugation with glutathione. The genes encoding the mu class of enzymes are organized in a gene cluster on chromosome 1p13.3 and are known to be highly polymorphic. These genetic variations can change an individual's susceptibility to carcinogens and toxins as well as affect the toxicity and efficacy of certain drugs. [provided by RefSeq, Jul 2008]

GSTM2 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=-1.01).

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
GSTM2	NM_000848.4 link	c.361-395A>T	intron_variant	Intron 5 of 7	ENST00000241337.9	NP_000839.1	P28161-1A0A384P5E9Q0D2I8
GSTM2	NM_001142368.2 link	c.361-395A>T	intron_variant	Intron 5 of 8		NP_001135840.1	P28161-2Q0D2I8
GSTM2	XR_007059236.1 link	n.923-395A>T	intron_variant	Intron 6 of 6
GSTM2	XR_007059237.1 link	n.947-395A>T	intron_variant	Intron 6 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSTM2	ENST00000241337.9 link	c.361-395A>T		intron_variant	Intron 5 of 7	1	NM_000848.4	ENSP00000241337.4		P28161-1

Frequencies

GnomAD3 genomes

AF:

0.912

AC:

138719

AN:

152122

Hom.:

63349

Cov.:

show subpopulations

Gnomad AFR

AF:

0.899

Gnomad AMI

AF:

0.854

Gnomad AMR

AF:

0.930

Gnomad ASJ

AF:

0.901

Gnomad EAS

AF:

0.998

Gnomad SAS

AF:

0.914

Gnomad FIN

AF:

0.880

Gnomad MID

AF:

0.880

Gnomad NFE

AF:

0.916

Gnomad OTH

AF:

0.909

GnomAD4 exome

AF:

0.920

AC:

21491

AN:

23356

Hom.:

9914

Cov.:

AF XY:

0.917

AC XY:

11180

AN XY:

12186

show subpopulations

Gnomad4 AFR exome

AF:

0.884

Gnomad4 AMR exome

AF:

0.946

Gnomad4 ASJ exome

AF:

0.888

Gnomad4 EAS exome

AF:

0.999

Gnomad4 SAS exome

AF:

0.911

Gnomad4 FIN exome

AF:

0.868

Gnomad4 NFE exome

AF:

0.913

Gnomad4 OTH exome

AF:

0.891

GnomAD4 genome

AF:

0.912

AC:

138836

AN:

152238

Hom.:

63405

Cov.:

AF XY:

0.910

AC XY:

67761

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.899

Gnomad4 AMR

AF:

0.930

Gnomad4 ASJ

AF:

0.901

Gnomad4 EAS

AF:

0.998

Gnomad4 SAS

AF:

0.914

Gnomad4 FIN

AF:

0.880

Gnomad4 NFE

AF:

0.916

Gnomad4 OTH

AF:

0.910

Alfa

AF:

0.880

Hom.:

2806

Bravo

AF:

0.918

Asia WGS

AF:

0.954

AC:

3319

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

2.3

DANN

Benign

0.66

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