rs17024661

Positions:

• chr1-109715742-A-G

Variant summary

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

The NM_000851.4(GSTM5):​c.567+502A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0362 in 413,860 control chromosomes in the GnomAD database, including 457 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 0.035 (117 hom., cov: 33)
  • Exomes 𝑓: 0.037 (340 hom.)
• Consequence: GSTM5 NM_000851.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0916 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GSTM5	NM_000851.4	c.567+502A>G		intron_variant		ENST00000256593.8
GSTM5	XM_005270784.5	c.567+502A>G		intron_variant
GSTM5	XM_005270785.5	c.255+502A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSTM5	ENST00000256593.8	c.567+502A>G		intron_variant		1	NM_000851.4	P3

Frequencies

GnomAD3 genomes AF: 0.0348 AC: 5297 AN: 152086 Hom.: 112 Cov.: 33

Gnomad AFR AF: 0.0490

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.0351

Gnomad ASJ AF: 0.0404

Gnomad EAS AF: 0.00270

Gnomad SAS AF: 0.0995

Gnomad FIN AF: 0.0118

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0271

Gnomad OTH AF: 0.0359

GnomAD4 exome AF: 0.0370 AC: 9671 AN: 261656 Hom.: 340 Cov.: 4 AF XY: 0.0421 AC XY: 6023 AN XY: 142972

Gnomad4 AFR exome AF: 0.0486

Gnomad4 AMR exome AF: 0.0393

Gnomad4 ASJ exome AF: 0.0433

Gnomad4 EAS exome AF: 0.000660

Gnomad4 SAS exome AF: 0.0990

Gnomad4 FIN exome AF: 0.0162

Gnomad4 NFE exome AF: 0.0247

Gnomad4 OTH exome AF: 0.0338

GnomAD4 genome AF: 0.0350 AC: 5320 AN: 152204 Hom.: 117 Cov.: 33 AF XY: 0.0340 AC XY: 2532 AN XY: 74412

Gnomad4 AFR AF: 0.0495

Gnomad4 AMR AF: 0.0350

Gnomad4 ASJ AF: 0.0404

Gnomad4 EAS AF: 0.00271

Gnomad4 SAS AF: 0.0990

Gnomad4 FIN AF: 0.0118

Gnomad4 NFE AF: 0.0271

Gnomad4 OTH AF: 0.0355

Alfa AF: 0.0320 Hom.: 81

Bravo AF: 0.0360

Asia WGS AF: 0.0470 AC: 165 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.47
DANN	Benign	0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs17024661; hg19: chr1-110258364;