NM_000848.4:c.361-395A>T

Variant names:

• chr1-109670892-A-T
• rs574344
• NM_000848.4:c.361-395A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.306
• Publications: 11 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 -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000848.4. 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.361-395A>T		intron	N/A	NP_000839.1
	GSTM2	NM_001142368.2		c.361-395A>T		intron	N/A	NP_001135840.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSTM2	ENST00000241337.9	TSL:1 MANE Select	c.361-395A>T		intron	N/A	ENSP00000241337.4
	GSTM2	ENST00000414179.6	TSL:1	c.49-395A>T		intron	N/A	ENSP00000404662.2
	GSTM2	ENST00000864527.1		c.634-395A>T		intron	N/A	ENSP00000534586.1

Frequencies

GnomAD3 genomes AF: 0.912 AC: 138719 AN: 152122 Hom.: 63349 Cov.: 32

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.: 0 AF XY: 0.917 AC XY: 11180 AN XY: 12186

African (AFR) AF: 0.884 AC: 764 AN: 864

American (AMR) AF: 0.946 AC: 2771 AN: 2930

Ashkenazi Jewish (ASJ) AF: 0.888 AC: 517 AN: 582

East Asian (EAS) AF: 0.999 AC: 1825 AN: 1826

South Asian (SAS) AF: 0.911 AC: 1828 AN: 2006

European-Finnish (FIN) AF: 0.868 AC: 441 AN: 508

Middle Eastern (MID) AF: 0.892 AC: 66 AN: 74

European-Non Finnish (NFE) AF: 0.913 AC: 12253 AN: 13414

Other (OTH) AF: 0.891 AC: 1026 AN: 1152

GnomAD4 genome AF: 0.912 AC: 138836 AN: 152238 Hom.: 63405 Cov.: 32 AF XY: 0.910 AC XY: 67761 AN XY: 74434

African (AFR) AF: 0.899 AC: 37329 AN: 41532

American (AMR) AF: 0.930 AC: 14225 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.901 AC: 3126 AN: 3470

East Asian (EAS) AF: 0.998 AC: 5181 AN: 5190

South Asian (SAS) AF: 0.914 AC: 4409 AN: 4824

European-Finnish (FIN) AF: 0.880 AC: 9317 AN: 10592

Middle Eastern (MID) AF: 0.888 AC: 261 AN: 294

European-Non Finnish (NFE) AF: 0.916 AC: 62289 AN: 68026

Other (OTH) AF: 0.910 AC: 1920 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.3
DANN	Benign	0.66
PhyloP100		0.31
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs574344; hg19: chr1-110213514; COSMIC: COSV53981950; COSMIC: COSV53981950;