1-109672556-A-G

Variant names:

• chr1-109672556-A-G
• rs655315
• NM_000848.4:c.567+973A>G

Variant summary

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

The NM_000848.4(GSTM2):​c.567+973A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.417 in 151,594 control chromosomes in the GnomAD database, including 14,815 homozygotes. 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 0.42 (14815 hom., cov: 32)
• Consequence: GSTM2 NM_000848.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21
• Publications: 13 publications found

Genes affected

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.66 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000848.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSTM2	NM_000848.4	MANE Select	c.567+973A>G		intron	N/A	NP_000839.1
	GSTM2	NM_001142368.2		c.567+973A>G		intron	N/A	NP_001135840.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSTM2	ENST00000241337.9	TSL:1 MANE Select	c.567+973A>G		intron	N/A	ENSP00000241337.4
	GSTM2	ENST00000414179.6	TSL:1	c.255+973A>G		intron	N/A	ENSP00000404662.2
	GSTM2	ENST00000369831.6	TSL:2	c.567+973A>G		intron	N/A	ENSP00000358846.2

Frequencies

GnomAD3 genomes AF: 0.417 AC: 63183 AN: 151478 Hom.: 14800 Cov.: 32

Gnomad AFR AF: 0.191

Gnomad AMI AF: 0.450

Gnomad AMR AF: 0.557

Gnomad ASJ AF: 0.479

Gnomad EAS AF: 0.679

Gnomad SAS AF: 0.469

Gnomad FIN AF: 0.461

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.488

Gnomad OTH AF: 0.459

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

GnomAD4 genome AF: 0.417 AC: 63215 AN: 151594 Hom.: 14815 Cov.: 32 AF XY: 0.420 AC XY: 31092 AN XY: 74074

African (AFR) AF: 0.191 AC: 7915 AN: 41470

American (AMR) AF: 0.557 AC: 8487 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.479 AC: 1655 AN: 3458

East Asian (EAS) AF: 0.678 AC: 3453 AN: 5090

South Asian (SAS) AF: 0.469 AC: 2262 AN: 4818

European-Finnish (FIN) AF: 0.461 AC: 4862 AN: 10544

Middle Eastern (MID) AF: 0.538 AC: 154 AN: 286

European-Non Finnish (NFE) AF: 0.488 AC: 33056 AN: 67710

Other (OTH) AF: 0.462 AC: 971 AN: 2104

Alfa AF: 0.472 Hom.: 52820

Bravo AF: 0.421

Asia WGS AF: 0.559 AC: 1948 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.88
DANN	Benign	0.83
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs655315; hg19: chr1-110215178;