rs592792

chr1-109669334-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.08

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]

ACMG classification

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	UniProt
GSTM2	NM_000848.4	c.222C>T	p.Asn74=	synonymous_variant	4/8	ENST00000241337.9
GSTM2	NM_001142368.2	c.222C>T	p.Asn74=	synonymous_variant	4/9
GSTM2	XR_007059236.1	n.281C>T		non_coding_transcript_exon_variant	4/7
GSTM2	XR_007059237.1	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	c.222C>T	p.Asn74=	synonymous_variant	4/8	1	NM_000848.4	P1

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20157 AN: 151992 Hom.: 1474 Cov.: 31

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

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.: 34 AF XY: 0.126 AC XY: 91326 AN XY: 727102

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.: 31 AF XY: 0.128 AC XY: 9539 AN XY: 74364

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

Other links and lift over

dbSNP: rs592792; hg19: chr1-110211956;