rs4147562

Variant names:

• chr1-109687477-A-T
• rs4147562
• ENST00000876523.1:c.-397A>T

Variant summary

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

The ENST00000876523.1(GSTM1):​c.-397A>T variant causes a 5 prime UTR 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 0.15 (1967 hom., cov: 15)
• Consequence: GSTM1 ENST00000876523.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00800
• Publications: 2 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=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.223 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000876523.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSTM1	ENST00000876523.1		c.-397A>T		5_prime_UTR	Exon 1 of 8	ENSP00000546582.1
	GSTM2	ENST00000369831.6	TSL:2	c.567+15894A>T		intron	N/A	ENSP00000358846.2
	GSTM1	ENST00000876522.1		c.-33+90A>T		intron	N/A	ENSP00000546581.1

Frequencies

GnomAD3 genomes AF: 0.148 AC: 13135 AN: 88706 Hom.: 1956 Cov.: 15

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.0838

Gnomad AMR AF: 0.199

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.134

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

GnomAD4 genome AF: 0.148 AC: 13155 AN: 88800 Hom.: 1967 Cov.: 15 AF XY: 0.147 AC XY: 6365 AN XY: 43246

African (AFR) AF: 0.132 AC: 3588 AN: 27086

American (AMR) AF: 0.200 AC: 1826 AN: 9152

Ashkenazi Jewish (ASJ) AF: 0.133 AC: 263 AN: 1972

East Asian (EAS) AF: 0.109 AC: 452 AN: 4138

South Asian (SAS) AF: 0.237 AC: 726 AN: 3060

European-Finnish (FIN) AF: 0.131 AC: 766 AN: 5826

Middle Eastern (MID) AF: 0.160 AC: 23 AN: 144

European-Non Finnish (NFE) AF: 0.148 AC: 5338 AN: 35972

Other (OTH) AF: 0.131 AC: 143 AN: 1092

Alfa AF: 0.260 Hom.: 765

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	6.1
DANN	Benign	0.21
PhyloP100		-0.0080
PromoterAI		0.0082	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4147562; hg19: chr1-110230099;