rs4147567

Variant names:

• chr1-109689902-A-G
• rs4147567
• NM_000561.4:c.361-369A>G

Variant summary

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

The NM_000561.4(GSTM1):​c.361-369A>G 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 0.088 (2516 hom., cov: 12)
• Consequence: GSTM1 NM_000561.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.596
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.22 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSTM1	NM_000561.4	c.361-369A>G		intron_variant	Intron 5 of 7	ENST00000309851.10	NP_000552.2
GSTM1	NM_146421.3	c.361-369A>G		intron_variant	Intron 5 of 6		NP_666533.1
GSTM1	XM_005270782.6	c.259-369A>G		intron_variant	Intron 5 of 7		XP_005270839.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSTM1	ENST00000309851.10	c.361-369A>G		intron_variant	Intron 5 of 7	1	NM_000561.4	ENSP00000311469.5

Frequencies

GnomAD3 genomes AF: 0.0877 AC: 7007 AN: 79942 Hom.: 2507 Cov.: 12

Gnomad AFR AF: 0.225

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0381

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00788

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0571

Gnomad NFE AF: 0.00290

Gnomad OTH AF: 0.0664

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0879 AC: 7034 AN: 80052 Hom.: 2516 Cov.: 12 AF XY: 0.0880 AC XY: 3426 AN XY: 38950

African (AFR) AF: 0.225 AC: 6282 AN: 27962

American (AMR) AF: 0.0380 AC: 284 AN: 7474

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1770

East Asian (EAS) AF: 0.00788 AC: 17 AN: 2156

South Asian (SAS) AF: 0.108 AC: 284 AN: 2640

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5220

Middle Eastern (MID) AF: 0.0615 AC: 8 AN: 130

European-Non Finnish (NFE) AF: 0.00290 AC: 91 AN: 31330

Other (OTH) AF: 0.0663 AC: 68 AN: 1026

Alfa AF: 0.00945 Hom.: 184

Asia WGS AF: 0.110 AC: 215 AN: 1912

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.1
DANN	Benign	0.67
PhyloP100		0.60
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: rs4147567; hg19: chr1-110232524;