rs412302

Variant names:

• chr1-109687394-G-A
• rs412302
• ENST00000876523.1:c.-480G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-109687394-G-A
• chr1-109687394-G-C

Variant summary

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

The ENST00000876522.1(GSTM1):​c.-33+7G>A variant causes a splice region, 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 0.36 (9467 hom., cov: 13)
• Consequence: GSTM1 ENST00000876522.1 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02
• Publications: 4 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000876522.1. 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.-480G>A		5_prime_UTR	Exon 1 of 8	ENSP00000546582.1
	GSTM2	ENST00000369831.6	TSL:2	c.567+15811G>A		intron	N/A	ENSP00000358846.2	F6XZQ7
	GSTM1	ENST00000876522.1		c.-33+7G>A		splice_region intron	N/A	ENSP00000546581.1

Frequencies

GnomAD3 genomes AF: 0.360 AC: 33174 AN: 92102 Hom.: 9456 Cov.: 13

Gnomad AFR AF: 0.427

Gnomad AMI AF: 0.136

Gnomad AMR AF: 0.416

Gnomad ASJ AF: 0.379

Gnomad EAS AF: 0.237

Gnomad SAS AF: 0.424

Gnomad FIN AF: 0.236

Gnomad MID AF: 0.330

Gnomad NFE AF: 0.335

Gnomad OTH AF: 0.368

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

GnomAD4 genome AF: 0.360 AC: 33216 AN: 92190 Hom.: 9467 Cov.: 13 AF XY: 0.356 AC XY: 15849 AN XY: 44494

African (AFR) AF: 0.427 AC: 10570 AN: 24770

American (AMR) AF: 0.417 AC: 3920 AN: 9408

Ashkenazi Jewish (ASJ) AF: 0.379 AC: 842 AN: 2224

East Asian (EAS) AF: 0.237 AC: 960 AN: 4046

South Asian (SAS) AF: 0.424 AC: 1296 AN: 3058

European-Finnish (FIN) AF: 0.236 AC: 1543 AN: 6540

Middle Eastern (MID) AF: 0.315 AC: 53 AN: 168

European-Non Finnish (NFE) AF: 0.336 AC: 13549 AN: 40382

Other (OTH) AF: 0.363 AC: 426 AN: 1174

Alfa AF: 0.398 Hom.: 1292

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.9
DANN	Benign	0.58
PhyloP100		-1.0
PromoterAI		-0.015	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs412302;

hg19: chr1-110230016;