rs592792

Variant names:

• chr1-109669334-C-T
• rs592792
• ENST00000414179.6:c.-91C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000414179.6(GSTM2):​c.-91C>T variant causes a 5 prime UTR premature start codon gain 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 ENST00000414179.6 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.08
• Publications: 14 publications found

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

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.163 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000414179.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSTM2	NM_000848.4	MANE Select	c.222C>T	p.Asn74Asn	synonymous	Exon 4 of 8	NP_000839.1
	GSTM2	NM_001142368.2		c.222C>T	p.Asn74Asn	synonymous	Exon 4 of 9	NP_001135840.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSTM2	ENST00000414179.6	TSL:1	c.-91C>T		5_prime_UTR_premature_start_codon_gain	Exon 4 of 9	ENSP00000404662.2
	GSTM2	ENST00000241337.9	TSL:1 MANE Select	c.222C>T	p.Asn74Asn	synonymous	Exon 4 of 8	ENSP00000241337.4
	GSTM2	ENST00000414179.6	TSL:1	c.-91C>T		5_prime_UTR	Exon 4 of 9	ENSP00000404662.2

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

GnomAD2 exomes AF: 0.104 AC: 26219 AN: 251496 AF XY: 0.104

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 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

African (AFR) AF: 0.170 AC: 5682 AN: 33470

American (AMR) AF: 0.0630 AC: 2816 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 3421 AN: 26134

East Asian (EAS) AF: 0.000378 AC: 15 AN: 39700

South Asian (SAS) AF: 0.0592 AC: 5109 AN: 86254

European-Finnish (FIN) AF: 0.112 AC: 5959 AN: 53420

Middle Eastern (MID) AF: 0.0863 AC: 498 AN: 5768

European-Non Finnish (NFE) AF: 0.140 AC: 155150 AN: 1111730

Other (OTH) AF: 0.117 AC: 7085 AN: 60390

GnomAD4 genome AF: 0.133 AC: 20187 AN: 152110 Hom.: 1478 Cov.: 31 AF XY: 0.128 AC XY: 9539 AN XY: 74364

African (AFR) AF: 0.166 AC: 6901 AN: 41462

American (AMR) AF: 0.0931 AC: 1424 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.129 AC: 448 AN: 3472

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5184

South Asian (SAS) AF: 0.0542 AC: 262 AN: 4830

European-Finnish (FIN) AF: 0.109 AC: 1150 AN: 10584

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.140 AC: 9536 AN: 67968

Other (OTH) AF: 0.121 AC: 255 AN: 2112

Alfa AF: 0.134 Hom.: 917

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	7.5
DANN	Benign	0.89
PhyloP100		-2.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs592792; hg19: chr1-110211956; COSMIC: COSV108059881; COSMIC: COSV108059881;