rs36208869

Variant names:

• chr1-109687656-T-C
• rs36208869
• ENST00000369831.6:c.567+16073T>C

Variant summary

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

The ENST00000369831.6(GSTM2):​c.567+16073T>C 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 0.20 (6519 hom., cov: 12)
• Consequence: GSTM2 ENST00000369831.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.57

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]

GSTM1 (HGNC:4632): (glutathione S-transferase mu 1) 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. Null mutations of this class mu gene have been linked with an increase in a number of cancers, likely due to an increased susceptibility to environmental toxins and carcinogens. Multiple protein isoforms are encoded by transcript variants of this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.234 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSTM1	NM_000561.4	c.-218T>C		upstream_gene_variant		ENST00000309851.10	NP_000552.2
GSTM1	NM_146421.3	c.-218T>C		upstream_gene_variant			NP_666533.1
GSTM1	XM_005270782.6	c.-373T>C		upstream_gene_variant			XP_005270839.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSTM1	ENST00000309851.10	c.-218T>C		upstream_gene_variant		1	NM_000561.4	ENSP00000311469.5

Frequencies

GnomAD3 genomes AF: 0.198 AC: 16112 AN: 81192 Hom.: 6514 Cov.: 12

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.270

Gnomad EAS AF: 0.00232

Gnomad SAS AF: 0.190

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.341

Gnomad NFE AF: 0.239

Gnomad OTH AF: 0.202

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

GnomAD4 genome AF: 0.198 AC: 16126 AN: 81306 Hom.: 6519 Cov.: 12 AF XY: 0.195 AC XY: 7740 AN XY: 39702

Gnomad4 AFR AF: 0.184

Gnomad4 AMR AF: 0.143

Gnomad4 ASJ AF: 0.270

Gnomad4 EAS AF: 0.00232

Gnomad4 SAS AF: 0.191

Gnomad4 FIN AF: 0.181

Gnomad4 NFE AF: 0.239

Gnomad4 OTH AF: 0.203

Alfa AF: 0.127 Hom.: 617

Asia WGS AF: 0.146 AC: 282 AN: 1908

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.5
DANN	Benign	0.30

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs36208869; hg19: chr1-110230278;