1-109712552-T-G

Variant names:

• chr1-109712552-T-G
• rs929166
• NM_000851.4:c.37-66T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000851.4(GSTM5):​c.37-66T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.298 in 1,569,484 control chromosomes in the GnomAD database, including 76,320 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 0.27 (6501 hom., cov: 32)
  • Exomes 𝑓: 0.30 (69819 hom.)
• Consequence: GSTM5 NM_000851.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.578
• Publications: 25 publications found

Genes affected

GSTM5 (HGNC:4637): (glutathione S-transferase mu 5) 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. [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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.675 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSTM5	NM_000851.4	c.37-66T>G		intron_variant	Intron 1 of 7	ENST00000256593.8	NP_000842.2
GSTM5	XM_005270784.5	c.37-66T>G		intron_variant	Intron 2 of 8		XP_005270841.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSTM5	ENST00000256593.8	c.37-66T>G		intron_variant	Intron 1 of 7	1	NM_000851.4	ENSP00000256593.3

Frequencies

GnomAD3 genomes AF: 0.268 AC: 40641 AN: 151748 Hom.: 6494 Cov.: 32

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.365

Gnomad ASJ AF: 0.272

Gnomad EAS AF: 0.695

Gnomad SAS AF: 0.340

Gnomad FIN AF: 0.311

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.271

GnomAD4 exome AF: 0.302 AC: 427665 AN: 1417622 Hom.: 69819 Cov.: 28 AF XY: 0.302 AC XY: 214125 AN XY: 707882

African (AFR) AF: 0.125 AC: 4090 AN: 32622

American (AMR) AF: 0.472 AC: 21085 AN: 44660

Ashkenazi Jewish (ASJ) AF: 0.271 AC: 7012 AN: 25844

East Asian (EAS) AF: 0.689 AC: 27180 AN: 39466

South Asian (SAS) AF: 0.346 AC: 29549 AN: 85354

European-Finnish (FIN) AF: 0.319 AC: 16970 AN: 53254

Middle Eastern (MID) AF: 0.253 AC: 1357 AN: 5372

European-Non Finnish (NFE) AF: 0.282 AC: 302630 AN: 1072238

Other (OTH) AF: 0.303 AC: 17792 AN: 58812

GnomAD4 genome AF: 0.268 AC: 40665 AN: 151862 Hom.: 6501 Cov.: 32 AF XY: 0.273 AC XY: 20225 AN XY: 74214

African (AFR) AF: 0.136 AC: 5656 AN: 41460

American (AMR) AF: 0.365 AC: 5568 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.272 AC: 943 AN: 3470

East Asian (EAS) AF: 0.694 AC: 3545 AN: 5110

South Asian (SAS) AF: 0.341 AC: 1642 AN: 4812

European-Finnish (FIN) AF: 0.311 AC: 3284 AN: 10552

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.283 AC: 19237 AN: 67884

Other (OTH) AF: 0.278 AC: 585 AN: 2106

Alfa AF: 0.286 Hom.: 14547

Bravo AF: 0.268

Asia WGS AF: 0.466 AC: 1619 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.9
DANN	Benign	0.42
PhyloP100		-0.58
PromoterAI		0.025	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs929166; hg19: chr1-110255174;