Variant chr1-109669334-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_000848.4(GSTM2):c.222C>T(p.Asn74=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 1,613,700 control chromosomes in the GnomAD database, including 14,267 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 0.13 ( 1478 hom., cov: 31)

Exomes 𝑓: 0.13 ( 12789 hom. )

Consequence

GSTM2
NM_000848.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.08

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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.31).

BP7

Synonymous conserved (PhyloP=-2.08 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.163 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
GSTM2	NM_000848.4 linkuse as main transcript	c.222C>T	p.Asn74=	synonymous_variant	4/8	ENST00000241337.9
GSTM2	NM_001142368.2 linkuse as main transcript	c.222C>T	p.Asn74=	synonymous_variant	4/9
GSTM2	XR_007059236.1 linkuse as main transcript	n.281C>T		non_coding_transcript_exon_variant	4/7
GSTM2	XR_007059237.1 linkuse as main transcript	n.281C>T		non_coding_transcript_exon_variant	4/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSTM2	ENST00000241337.9 linkuse as main transcript	c.222C>T	p.Asn74=	synonymous_variant	4/8	1	NM_000848.4	P1	P28161-1

Frequencies

GnomAD3 genomes

AF:

0.133

AC:

20157

AN:

151992

Hom.:

1474

Cov.:

show subpopulations

Gnomad AFR

AF:

0.166

Gnomad AMI

AF:

0.184

Gnomad AMR

AF:

0.0933

Gnomad ASJ

AF:

0.129

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.0540

Gnomad FIN

AF:

0.109

Gnomad MID

AF:

0.133

Gnomad NFE

AF:

0.140

Gnomad OTH

AF:

0.122

GnomAD3 exomes

AF:

0.104

AC:

26219

AN:

251496

Hom.:

1669

AF XY:

0.104

AC XY:

14173

AN XY:

135922

show subpopulations

Gnomad AFR exome

AF:

0.166

Gnomad AMR exome

AF:

0.0588

Gnomad ASJ exome

AF:

0.132

Gnomad EAS exome

AF:

0.000544

Gnomad SAS exome

AF:

0.0590

Gnomad FIN exome

AF:

0.109

Gnomad NFE exome

AF:

0.134

Gnomad OTH exome

AF:

0.112

GnomAD4 exome

AF:

0.127

AC:

185735

AN:

1461590

Hom.:

12789

Cov.:

AF XY:

0.126

AC XY:

91326

AN XY:

727102

show subpopulations

Gnomad4 AFR exome

AF:

0.170

Gnomad4 AMR exome

AF:

0.0630

Gnomad4 ASJ exome

AF:

0.131

Gnomad4 EAS exome

AF:

0.000378

Gnomad4 SAS exome

AF:

0.0592

Gnomad4 FIN exome

AF:

0.112

Gnomad4 NFE exome

AF:

0.140

Gnomad4 OTH exome

AF:

0.117

GnomAD4 genome

AF:

0.133

AC:

20187

AN:

152110

Hom.:

1478

Cov.:

AF XY:

0.128

AC XY:

9539

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.166

Gnomad4 AMR

AF:

0.0931

Gnomad4 ASJ

AF:

0.129

Gnomad4 EAS

AF:

0.000772

Gnomad4 SAS

AF:

0.0542

Gnomad4 FIN

AF:

0.109

Gnomad4 NFE

AF:

0.140

Gnomad4 OTH

AF:

0.121

Alfa

AF:

0.138

Hom.:

689

Bravo

AF:

0.135

Asia WGS

AF:

0.0380

AC:

137

AN:

3478

EpiCase

AF:

0.139

EpiControl

AF:

0.132

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.31

CADD

Benign

7.5

DANN

Benign

0.89

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

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