rs17024661

Variant names:

• chr1-109715742-A-G
• rs17024661
• NM_000851.4:c.567+502A>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.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
• Publications: 5 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=-0.92).
• 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 rank	MANE	Protein	UniProt
GSTM5	NM_000851.4	c.567+502A>G		intron_variant	Intron 7 of 7	ENST00000256593.8	NP_000842.2
GSTM5	XM_005270784.5	c.567+502A>G		intron_variant	Intron 8 of 8		XP_005270841.1
GSTM5	XM_005270785.5	c.255+502A>G		intron_variant	Intron 4 of 4		XP_005270842.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSTM5	ENST00000256593.8	c.567+502A>G		intron_variant	Intron 7 of 7	1	NM_000851.4	ENSP00000256593.3

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

African (AFR) AF: 0.0486 AC: 368 AN: 7572

American (AMR) AF: 0.0393 AC: 422 AN: 10732

Ashkenazi Jewish (ASJ) AF: 0.0433 AC: 300 AN: 6936

East Asian (EAS) AF: 0.000660 AC: 8 AN: 12124

South Asian (SAS) AF: 0.0990 AC: 3927 AN: 39682

European-Finnish (FIN) AF: 0.0162 AC: 174 AN: 10722

Middle Eastern (MID) AF: 0.0682 AC: 72 AN: 1056

European-Non Finnish (NFE) AF: 0.0247 AC: 3928 AN: 158872

Other (OTH) AF: 0.0338 AC: 472 AN: 13960

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

African (AFR) AF: 0.0495 AC: 2056 AN: 41526

American (AMR) AF: 0.0350 AC: 536 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0404 AC: 140 AN: 3468

East Asian (EAS) AF: 0.00271 AC: 14 AN: 5170

South Asian (SAS) AF: 0.0990 AC: 475 AN: 4800

European-Finnish (FIN) AF: 0.0118 AC: 125 AN: 10600

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0271 AC: 1842 AN: 68022

Other (OTH) AF: 0.0355 AC: 75 AN: 2112

Alfa AF: 0.0323 Hom.: 95

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
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17024661; hg19: chr1-110258364;