rs2073483

chr1-109668196-C-Gchr1-109668196-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000848.4(GSTM2):c.36+45C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000774 in 1,343,928 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00011 (0 hom., cov: 29)
  • Exomes 𝑓: 0.000074 (0 hom.)
• Consequence: GSTM2 NM_000848.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.51

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GSTM2	NM_000848.4	c.36+45C>G		intron_variant		ENST00000241337.9
GSTM2	NM_001142368.2	c.36+45C>G		intron_variant
GSTM2	XR_007059236.1	n.95+45C>G		intron_variant, non_coding_transcript_variant
GSTM2	XR_007059237.1	n.95+45C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSTM2	ENST00000241337.9	c.36+45C>G		intron_variant		1	NM_000848.4	P1

Frequencies

GnomAD3 genomes AF: 0.000107 AC: 16 AN: 149288 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.0000991

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000266

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000983

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000104

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000214 AC: 5 AN: 233524 Hom.: 0 AF XY: 0.0000156 AC XY: 2 AN XY: 128238

Gnomad AFR exome AF: 0.000295

Gnomad AMR exome AF: 0.0000297

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000737 AC: 88 AN: 1194530 Hom.: 0 Cov.: 21 AF XY: 0.0000726 AC XY: 44 AN XY: 605796

Gnomad4 AFR exome AF: 0.000215

Gnomad4 AMR exome AF: 0.0000458

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000261

Gnomad4 SAS exome AF: 0.0000371

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000835

Gnomad4 OTH exome AF: 0.0000587

GnomAD4 genome AF: 0.000107 AC: 16 AN: 149398 Hom.: 0 Cov.: 29 AF XY: 0.0000959 AC XY: 7 AN XY: 72956

Gnomad4 AFR AF: 0.0000988

Gnomad4 AMR AF: 0.000265

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000983

Gnomad4 NFE AF: 0.000104

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000470 Hom.: 1365

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.39
Dann	Benign	0.16

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: rs2073483; hg19: chr1-110210818;