ENST00000369831.6:c.568-5067G>C

Variant names:

• chr1-109703414-G-C
• rs11101985
• ENST00000369831.6:c.568-5067G>C

Variant summary

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

The ENST00000369831.6(GSTM2):​c.568-5067G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.341 in 151,674 control chromosomes in the GnomAD database, including 10,957 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 0.34 (10957 hom., cov: 31)
• Consequence: GSTM2 ENST00000369831.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.678 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.568-5067G>C		intron_variant	Intron 7 of 7	2		ENSP00000358846.2
GSTM1	ENST00000483399.6	c.*21-5067G>C		intron_variant	Intron 4 of 4	3		ENSP00000455929.1
GSTM1	ENST00000490021.2	n.345-5067G>C		intron_variant	Intron 4 of 4	3

Frequencies

GnomAD3 genomes AF: 0.341 AC: 51642 AN: 151556 Hom.: 10952 Cov.: 31

Gnomad AFR AF: 0.0903

Gnomad AMI AF: 0.222

Gnomad AMR AF: 0.448

Gnomad ASJ AF: 0.457

Gnomad EAS AF: 0.698

Gnomad SAS AF: 0.424

Gnomad FIN AF: 0.432

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.416

Gnomad OTH AF: 0.376

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

GnomAD4 genome AF: 0.341 AC: 51646 AN: 151674 Hom.: 10957 Cov.: 31 AF XY: 0.345 AC XY: 25601 AN XY: 74108

Gnomad4 AFR AF: 0.0901

Gnomad4 AMR AF: 0.447

Gnomad4 ASJ AF: 0.457

Gnomad4 EAS AF: 0.697

Gnomad4 SAS AF: 0.425

Gnomad4 FIN AF: 0.432

Gnomad4 NFE AF: 0.416

Gnomad4 OTH AF: 0.383

Alfa AF: 0.249 Hom.: 682

Bravo AF: 0.332

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.23
DANN	Benign	0.57

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11101985; hg19: chr1-110246036;