rs638820

Variant names:

• chr1-109667284-G-A
• rs638820
• XR_007059238.1:n.2100G>A

Variant summary

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

The XR_007059238.1(GSTM4):​n.2100G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.523 in 151,046 control chromosomes in the GnomAD database, including 20,814 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 0.52 (20814 hom., cov: 31)
• Consequence: GSTM4 XR_007059238.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.94

Genes affected

GSTM4 (HGNC:4636): (glutathione S-transferase mu 4) 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. Diversification of these genes has occurred in regions encoding substrate-binding domains, as well as in tissue expression patterns, to accommodate an increasing number of foreign compounds. Multiple transcript variants, each encoding a distinct protein isoform, have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.638 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSTM4	XR_007059238.1	n.2100G>A		non_coding_transcript_exon_variant	Exon 9 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.523 AC: 78947 AN: 150952 Hom.: 20792 Cov.: 31

Gnomad AFR AF: 0.511

Gnomad AMI AF: 0.372

Gnomad AMR AF: 0.611

Gnomad ASJ AF: 0.529

Gnomad EAS AF: 0.656

Gnomad SAS AF: 0.461

Gnomad FIN AF: 0.511

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.507

Gnomad OTH AF: 0.556

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

GnomAD4 genome AF: 0.523 AC: 79009 AN: 151046 Hom.: 20814 Cov.: 31 AF XY: 0.524 AC XY: 38664 AN XY: 73822

Gnomad4 AFR AF: 0.511

Gnomad4 AMR AF: 0.611

Gnomad4 ASJ AF: 0.529

Gnomad4 EAS AF: 0.656

Gnomad4 SAS AF: 0.461

Gnomad4 FIN AF: 0.511

Gnomad4 NFE AF: 0.507

Gnomad4 OTH AF: 0.557

Alfa AF: 0.510 Hom.: 11690

Bravo AF: 0.535

Asia WGS AF: 0.573 AC: 1990 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.090
DANN	Benign	0.17

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs638820; hg19: chr1-110209906; COSMIC: COSV53981927; COSMIC: COSV53981927;