rs4147561

Variant names:

• chr1-109687476-C-T
• rs4147561
• ENST00000369831.6:c.567+15893C>T

Variant summary

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

The ENST00000369831.6(GSTM2):​c.567+15893C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.15 (1972 hom., cov: 15)
• Consequence: GSTM2 ENST00000369831.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.65
• Publications: 4 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=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.223 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSTM2	ENST00000369831.6	c.567+15893C>T		intron_variant	Intron 7 of 7	2		ENSP00000358846.2
GSTM2	ENST00000460717.8	c.*17+5642C>T		intron_variant	Intron 8 of 8	2		ENSP00000435910.2

Frequencies

GnomAD3 genomes AF: 0.149 AC: 13211 AN: 88802 Hom.: 1961 Cov.: 15

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.0824

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.167

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.133

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

GnomAD4 genome AF: 0.149 AC: 13232 AN: 88904 Hom.: 1972 Cov.: 15 AF XY: 0.148 AC XY: 6406 AN XY: 43300

African (AFR) AF: 0.133 AC: 3594 AN: 27108

American (AMR) AF: 0.201 AC: 1841 AN: 9174

Ashkenazi Jewish (ASJ) AF: 0.133 AC: 263 AN: 1972

East Asian (EAS) AF: 0.109 AC: 452 AN: 4134

South Asian (SAS) AF: 0.237 AC: 727 AN: 3062

European-Finnish (FIN) AF: 0.133 AC: 774 AN: 5824

Middle Eastern (MID) AF: 0.155 AC: 23 AN: 148

European-Non Finnish (NFE) AF: 0.149 AC: 5387 AN: 36036

Other (OTH) AF: 0.130 AC: 142 AN: 1094

Alfa AF: 0.260 Hom.: 763

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.049
DANN	Benign	0.87
PhyloP100		-3.6
PromoterAI		0.012	Neutral
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: rs4147561; hg19: chr1-110230098;