rs4147562

Positions:

• chr1-109687477-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000369831.6(GSTM2):​c.567+15894A>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 (1967 hom., cov: 15)
• Consequence: GSTM2 ENST00000369831.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00800

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• 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/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSTM2	ENST00000369831.6	c.567+15894A>T		intron_variant		2		ENSP00000358846
GSTM2	ENST00000460717.7	c.*17+5643A>T		intron_variant		2		ENSP00000435910

Frequencies

GnomAD3 genomes AF: 0.148 AC: 13135 AN: 88706 Hom.: 1956 Cov.: 15

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.0838

Gnomad AMR AF: 0.199

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.134

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

GnomAD4 genome AF: 0.148 AC: 13155 AN: 88800 Hom.: 1967 Cov.: 15 AF XY: 0.147 AC XY: 6365 AN XY: 43246

Gnomad4 AFR AF: 0.132

Gnomad4 AMR AF: 0.200

Gnomad4 ASJ AF: 0.133

Gnomad4 EAS AF: 0.109

Gnomad4 SAS AF: 0.237

Gnomad4 FIN AF: 0.131

Gnomad4 NFE AF: 0.148

Gnomad4 OTH AF: 0.131

Alfa AF: 0.260 Hom.: 765

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	6.1
DANN	Benign	0.21

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4147562; hg19: chr1-110230099;