1-109716394-G-T

Variant names:

• chr1-109716394-G-T
• rs3768490
• NM_000851.4:c.568-943G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.681 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000851.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSTM5	NM_000851.4	MANE Select	c.568-943G>T		intron	N/A	NP_000842.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSTM5	ENST00000256593.8	TSL:1 MANE Select	c.568-943G>T		intron	N/A	ENSP00000256593.3	P46439
	GSTM5	ENST00000878690.1		c.646-943G>T		intron	N/A	ENSP00000548749.1
	GSTM5	ENST00000966870.1		c.646-943G>T		intron	N/A	ENSP00000636929.1

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

African (AFR) AF: 0.0469 AC: 3 AN: 64

American (AMR) AF: 0.445 AC: 73 AN: 164

Ashkenazi Jewish (ASJ) AF: 0.333 AC: 34 AN: 102

East Asian (EAS) AF: 0.595 AC: 44 AN: 74

South Asian (SAS) AF: 0.472 AC: 154 AN: 326

European-Finnish (FIN) AF: 0.347 AC: 66 AN: 190

Middle Eastern (MID) AF: 0.455 AC: 10 AN: 22

European-Non Finnish (NFE) AF: 0.346 AC: 1277 AN: 3690

Other (OTH) AF: 0.343 AC: 87 AN: 254

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

African (AFR) AF: 0.113 AC: 4685 AN: 41552

American (AMR) AF: 0.374 AC: 5725 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.363 AC: 1260 AN: 3468

East Asian (EAS) AF: 0.700 AC: 3619 AN: 5172

South Asian (SAS) AF: 0.454 AC: 2188 AN: 4822

European-Finnish (FIN) AF: 0.343 AC: 3639 AN: 10596

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.338 AC: 22957 AN: 67992

Other (OTH) AF: 0.318 AC: 671 AN: 2108

Alfa AF: 0.297 Hom.: 949

Bravo AF: 0.291

Asia WGS AF: 0.510 AC: 1771 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.3
DANN	Benign	0.51
PhyloP100		0.017
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: rs3768490; hg19: chr1-110259016; COSMIC: COSV56657110;