1-109716394-G-T

Position:

• chr1-109716394-G-T

Variant summary

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

The NM_000851.4(GSTM5):​c.568-943G>T 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 157,092 control chromosomes in the GnomAD database, including 8,494 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 0.30 (8156 hom., cov: 33)
  • Exomes 𝑓: 0.36 (338 hom.)
• Consequence: GSTM5 NM_000851.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0170

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]

GSTM5 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.681 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GSTM5	NM_000851.4	c.568-943G>T		intron_variant		ENST00000256593.8	NP_000842.2
GSTM5	XM_005270784.5	c.568-943G>T		intron_variant			XP_005270841.1
GSTM5	XM_005270785.5	c.256-943G>T		intron_variant			XP_005270842.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSTM5	ENST00000256593.8	c.568-943G>T		intron_variant		1	NM_000851.4	ENSP00000256593.3

Frequencies

GnomAD3 genomes AF: 0.296 AC: 44983 AN: 152088 Hom.: 8151 Cov.: 33

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.190

Gnomad AMR AF: 0.375

Gnomad ASJ AF: 0.363

Gnomad EAS AF: 0.701

Gnomad SAS AF: 0.453

Gnomad FIN AF: 0.343

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.338

Gnomad OTH AF: 0.313

GnomAD4 exome AF: 0.358 AC: 1748 AN: 4886 Hom.: 338 Cov.: 0 AF XY: 0.374 AC XY: 996 AN XY: 2662

Gnomad4 AFR exome AF: 0.0469

Gnomad4 AMR exome AF: 0.445

Gnomad4 ASJ exome AF: 0.333

Gnomad4 EAS exome AF: 0.595

Gnomad4 SAS exome AF: 0.472

Gnomad4 FIN exome AF: 0.347

Gnomad4 NFE exome AF: 0.346

Gnomad4 OTH exome AF: 0.343

GnomAD4 genome AF: 0.296 AC: 45014 AN: 152206 Hom.: 8156 Cov.: 33 AF XY: 0.299 AC XY: 22267 AN XY: 74406

Gnomad4 AFR AF: 0.113

Gnomad4 AMR AF: 0.374

Gnomad4 ASJ AF: 0.363

Gnomad4 EAS AF: 0.700

Gnomad4 SAS AF: 0.454

Gnomad4 FIN AF: 0.343

Gnomad4 NFE AF: 0.338

Gnomad4 OTH AF: 0.318

Alfa AF: 0.307 Hom.: 947

Bravo AF: 0.291

Asia WGS AF: 0.510 AC: 1771 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.3
DANN	Benign	0.51

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

Publications

LitVar

Other links and lift over

dbSNP: rs3768490; hg19: chr1-110259016; COSMIC: COSV56657110;