rs638820

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 publications found

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

Our verdict: Benign. The variant received -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

African (AFR) AF: 0.511 AC: 21087 AN: 41232

American (AMR) AF: 0.611 AC: 9293 AN: 15200

Ashkenazi Jewish (ASJ) AF: 0.529 AC: 1834 AN: 3468

East Asian (EAS) AF: 0.656 AC: 3381 AN: 5152

South Asian (SAS) AF: 0.461 AC: 2206 AN: 4790

European-Finnish (FIN) AF: 0.511 AC: 5163 AN: 10112

Middle Eastern (MID) AF: 0.620 AC: 181 AN: 292

European-Non Finnish (NFE) AF: 0.507 AC: 34353 AN: 67784

Other (OTH) AF: 0.557 AC: 1172 AN: 2104

Alfa AF: 0.513 Hom.: 16155

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
PhyloP100		-1.9

Splicing

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

Other links and lift over

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