1-109688970-T-C

Position:

• chr1-109688970-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
GSTM1	NM_000561.4	c.178-78T>C		intron_variant		ENST00000309851.10	NP_000552.2
GSTM1	NM_146421.3	c.178-78T>C		intron_variant			NP_666533.1
GSTM1	XM_005270782.6	c.76-78T>C		intron_variant			XP_005270839.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSTM1	ENST00000309851.10	c.178-78T>C		intron_variant		1	NM_000561.4	ENSP00000311469	P1

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

GnomAD3 exomes AF: 0.364 AC: 47683 AN: 131052 Hom.: 21050 AF XY: 0.354 AC XY: 24933 AN XY: 70428

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 SAS exome AF: 0.213

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

Gnomad4 AFR exome AF: 0.188

Gnomad4 AMR exome AF: 0.462

Gnomad4 ASJ exome AF: 0.383

Gnomad4 EAS exome AF: 0.684

Gnomad4 SAS exome AF: 0.208

Gnomad4 FIN exome AF: 0.452

Gnomad4 NFE exome AF: 0.355

Gnomad4 OTH exome AF: 0.336

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

Gnomad4 AFR AF: 0.183

Gnomad4 AMR AF: 0.374

Gnomad4 ASJ AF: 0.395

Gnomad4 EAS AF: 0.650

Gnomad4 SAS AF: 0.219

Gnomad4 FIN AF: 0.422

Gnomad4 NFE AF: 0.353

Gnomad4 OTH AF: 0.329

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs737497; hg19: chr1-110231592; COSMIC: COSV59166566; COSMIC: COSV59166566;