1-109688970-T-C

Variant names:

• chr1-109688970-T-C
• rs737497
• NM_000561.4:c.178-78T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000561.4(GSTM1):​c.178-78T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 (10354 hom., cov: 12)
  • Exomes 𝑓: 0.36 (86114 hom.)
• Consequence: GSTM1 NM_000561.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.415
• Publications: 7 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.621 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSTM1	NM_000561.4	c.178-78T>C		intron_variant	Intron 3 of 7	ENST00000309851.10	NP_000552.2
GSTM1	NM_146421.3	c.178-78T>C		intron_variant	Intron 3 of 6		NP_666533.1
GSTM1	XM_005270782.6	c.76-78T>C		intron_variant	Intron 3 of 7		XP_005270839.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSTM1	ENST00000309851.10	c.178-78T>C		intron_variant	Intron 3 of 7	1	NM_000561.4	ENSP00000311469.5

Frequencies

GnomAD3 genomes AF: 0.302 AC: 24445 AN: 80908 Hom.: 10345 Cov.: 12

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.0858

Gnomad AMR AF: 0.373

Gnomad ASJ AF: 0.395

Gnomad EAS AF: 0.648

Gnomad SAS AF: 0.218

Gnomad FIN AF: 0.422

Gnomad MID AF: 0.303

Gnomad NFE AF: 0.353

Gnomad OTH AF: 0.330

GnomAD2 exomes AF: 0.364 AC: 47683 AN: 131052 AF XY: 0.354

Gnomad AFR exome AF: 0.181

Gnomad AMR exome AF: 0.473

Gnomad ASJ exome AF: 0.382

Gnomad EAS exome AF: 0.631

Gnomad FIN exome AF: 0.446

Gnomad NFE exome AF: 0.358

Gnomad OTH exome AF: 0.367

GnomAD4 exome AF: 0.356 AC: 199155 AN: 559844 Hom.: 86114 Cov.: 0 AF XY: 0.348 AC XY: 100071 AN XY: 287210

African (AFR) AF: 0.188 AC: 3909 AN: 20770

American (AMR) AF: 0.462 AC: 11402 AN: 24692

Ashkenazi Jewish (ASJ) AF: 0.383 AC: 4729 AN: 12344

East Asian (EAS) AF: 0.684 AC: 11857 AN: 17334

South Asian (SAS) AF: 0.208 AC: 10062 AN: 48294

European-Finnish (FIN) AF: 0.452 AC: 13052 AN: 28852

Middle Eastern (MID) AF: 0.297 AC: 569 AN: 1918

European-Non Finnish (NFE) AF: 0.355 AC: 135269 AN: 380906

Other (OTH) AF: 0.336 AC: 8306 AN: 24734

GnomAD4 genome AF: 0.302 AC: 24472 AN: 81022 Hom.: 10354 Cov.: 12 AF XY: 0.304 AC XY: 12029 AN XY: 39536

African (AFR) AF: 0.183 AC: 5220 AN: 28576

American (AMR) AF: 0.374 AC: 2870 AN: 7680

Ashkenazi Jewish (ASJ) AF: 0.395 AC: 696 AN: 1760

East Asian (EAS) AF: 0.650 AC: 1388 AN: 2136

South Asian (SAS) AF: 0.219 AC: 586 AN: 2680

European-Finnish (FIN) AF: 0.422 AC: 2236 AN: 5300

Middle Eastern (MID) AF: 0.273 AC: 36 AN: 132

European-Non Finnish (NFE) AF: 0.353 AC: 11064 AN: 31366

Other (OTH) AF: 0.329 AC: 347 AN: 1054

Alfa AF: 0.353 Hom.: 888

Asia WGS AF: 0.362 AC: 692 AN: 1918

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.6
DANN	Benign	0.45
PhyloP100		0.41
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs737497; hg19: chr1-110231592; COSMIC: COSV59166566; COSMIC: COSV59166566;