rs1056806

Variant names:

• chr1-109690525-C-T
• rs1056806
• NM_000561.4:c.528C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_000561.4(GSTM1):​c.528C>T​(p.Asp176Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 927,760 control chromosomes in the GnomAD database, including 51,388 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 (8706 hom., cov: 11)
  • Exomes 𝑓: 0.16 (42682 hom.)
• Consequence: GSTM1 NM_000561.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.41
• Publications: 31 publications found

Genes affected

GSTM1 (HGNC:4632): (glutathione S-transferase mu 1) 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. Null mutations of this class mu gene have been linked with an increase in a number of cancers, likely due to an increased susceptibility to environmental toxins and carcinogens. Multiple protein isoforms are encoded by transcript variants of this gene. [provided by RefSeq, Jul 2008]

GSTM2 (HGNC:4634): (glutathione S-transferase mu 2) 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. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP7: Synonymous conserved (PhyloP=-5.41 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.362 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSTM1	NM_000561.4	c.528C>T	p.Asp176Asp	synonymous_variant	Exon 7 of 8	ENST00000309851.10	NP_000552.2
GSTM1	XM_005270782.6	c.426C>T	p.Asp142Asp	synonymous_variant	Exon 7 of 8		XP_005270839.1
GSTM1	NM_146421.3	c.456+159C>T		intron_variant	Intron 6 of 6		NP_666533.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSTM1	ENST00000309851.10	c.528C>T	p.Asp176Asp	synonymous_variant	Exon 7 of 8	1	NM_000561.4	ENSP00000311469.5

Frequencies

GnomAD3 genomes AF: 0.268 AC: 21363 AN: 79712 Hom.: 8692 Cov.: 11

Gnomad AFR AF: 0.322

Gnomad AMI AF: 0.167

Gnomad AMR AF: 0.364

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.339

Gnomad SAS AF: 0.384

Gnomad FIN AF: 0.104

Gnomad MID AF: 0.181

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.290

GnomAD2 exomes AF: 0.192 AC: 33492 AN: 174206 AF XY: 0.190

Gnomad AFR exome AF: 0.251

Gnomad AMR exome AF: 0.293

Gnomad ASJ exome AF: 0.0888

Gnomad EAS exome AF: 0.284

Gnomad FIN exome AF: 0.0745

Gnomad NFE exome AF: 0.138

Gnomad OTH exome AF: 0.184

GnomAD4 exome AF: 0.165 AC: 139582 AN: 847932 Hom.: 42682 Cov.: 21 AF XY: 0.168 AC XY: 72069 AN XY: 428030

African (AFR) AF: 0.238 AC: 6537 AN: 27440

American (AMR) AF: 0.304 AC: 8833 AN: 29078

Ashkenazi Jewish (ASJ) AF: 0.112 AC: 1800 AN: 16142

East Asian (EAS) AF: 0.269 AC: 5493 AN: 20388

South Asian (SAS) AF: 0.333 AC: 18883 AN: 56634

European-Finnish (FIN) AF: 0.108 AC: 3528 AN: 32812

Middle Eastern (MID) AF: 0.194 AC: 579 AN: 2978

European-Non Finnish (NFE) AF: 0.139 AC: 87377 AN: 627688

Other (OTH) AF: 0.188 AC: 6552 AN: 34772

GnomAD4 genome AF: 0.268 AC: 21404 AN: 79828 Hom.: 8706 Cov.: 11 AF XY: 0.266 AC XY: 10310 AN XY: 38734

African (AFR) AF: 0.322 AC: 8994 AN: 27912

American (AMR) AF: 0.364 AC: 2717 AN: 7458

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 261 AN: 1774

East Asian (EAS) AF: 0.338 AC: 717 AN: 2124

South Asian (SAS) AF: 0.381 AC: 1001 AN: 2626

European-Finnish (FIN) AF: 0.104 AC: 543 AN: 5212

Middle Eastern (MID) AF: 0.192 AC: 25 AN: 130

European-Non Finnish (NFE) AF: 0.217 AC: 6790 AN: 31220

Other (OTH) AF: 0.290 AC: 300 AN: 1036

Alfa AF: 0.0879 Hom.: 806

Asia WGS AF: 0.352 AC: 690 AN: 1968

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.49
DANN	Benign	0.81
PhyloP100		-5.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1056806; hg19: chr1-110233147; COSMIC: COSV59166436; COSMIC: COSV59166436;