rs12024479

Variant names:

• chr1-109677464-C-G
• rs12024479
• ENST00000414179.6:c.256-4345C>G

Variant summary

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

The ENST00000414179.6(GSTM2):​c.256-4345C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.394 in 152,088 control chromosomes in the GnomAD database, including 12,535 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 0.39 (12535 hom., cov: 33)
• Consequence: GSTM2 ENST00000414179.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.107
• Publications: 8 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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.47 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_001142368.2		c.568-4345C>G		intron	N/A	NP_001135840.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSTM2	ENST00000414179.6	TSL:1	c.256-4345C>G		intron	N/A	ENSP00000404662.2
	GSTM2	ENST00000369831.6	TSL:2	c.567+5881C>G		intron	N/A	ENSP00000358846.2
	GSTM2	ENST00000442650.5	TSL:5	c.568-4345C>G		intron	N/A	ENSP00000416883.1

Frequencies

GnomAD3 genomes AF: 0.394 AC: 59900 AN: 151970 Hom.: 12533 Cov.: 33

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.435

Gnomad AMR AF: 0.363

Gnomad ASJ AF: 0.450

Gnomad EAS AF: 0.308

Gnomad SAS AF: 0.407

Gnomad FIN AF: 0.463

Gnomad MID AF: 0.315

Gnomad NFE AF: 0.474

Gnomad OTH AF: 0.400

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.394 AC: 59915 AN: 152088 Hom.: 12535 Cov.: 33 AF XY: 0.392 AC XY: 29172 AN XY: 74344

African (AFR) AF: 0.260 AC: 10793 AN: 41482

American (AMR) AF: 0.363 AC: 5536 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.450 AC: 1561 AN: 3472

East Asian (EAS) AF: 0.309 AC: 1596 AN: 5168

South Asian (SAS) AF: 0.406 AC: 1957 AN: 4824

European-Finnish (FIN) AF: 0.463 AC: 4888 AN: 10558

Middle Eastern (MID) AF: 0.308 AC: 90 AN: 292

European-Non Finnish (NFE) AF: 0.474 AC: 32255 AN: 68002

Other (OTH) AF: 0.399 AC: 843 AN: 2112

Alfa AF: 0.421 Hom.: 1733

Bravo AF: 0.379

Asia WGS AF: 0.340 AC: 1181 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.7
DANN	Benign	0.32
PhyloP100		0.11
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs12024479; hg19: chr1-110220086; COSMIC: COSV53981974; COSMIC: COSV53981974;