chr1-109676139-G-C

Variant names:

• chr1-109676139-G-C
• rs619686
• ENST00000414179.6:c.255+4556G>C

Variant summary

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

The NM_001142368.2(GSTM2):​c.567+4556G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.959 in 152,254 control chromosomes in the GnomAD database, including 70,118 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 0.96 (70118 hom., cov: 32)
• Consequence: GSTM2 NM_001142368.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08
• Publications: 5 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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.979 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142368.2. 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
	GSTM2	NM_001142368.2		c.567+4556G>C		intron	N/A	NP_001135840.1	P28161-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSTM2	ENST00000414179.6	TSL:1	c.255+4556G>C		intron	N/A	ENSP00000404662.2	E9PGV1
	GSTM2	ENST00000369831.6	TSL:2	c.567+4556G>C		intron	N/A	ENSP00000358846.2	F6XZQ7
	GSTM2	ENST00000442650.5	TSL:5	c.567+4556G>C		intron	N/A	ENSP00000416883.1	P28161-2

Frequencies

GnomAD3 genomes AF: 0.959 AC: 145944 AN: 152136 Hom.: 70055 Cov.: 32

Gnomad AFR AF: 0.987

Gnomad AMI AF: 0.966

Gnomad AMR AF: 0.948

Gnomad ASJ AF: 0.924

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.919

Gnomad FIN AF: 0.964

Gnomad MID AF: 0.902

Gnomad NFE AF: 0.947

Gnomad OTH AF: 0.939

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

GnomAD4 genome AF: 0.959 AC: 146068 AN: 152254 Hom.: 70118 Cov.: 32 AF XY: 0.959 AC XY: 71405 AN XY: 74438

African (AFR) AF: 0.987 AC: 41004 AN: 41558

American (AMR) AF: 0.948 AC: 14506 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.924 AC: 3207 AN: 3470

East Asian (EAS) AF: 0.998 AC: 5171 AN: 5180

South Asian (SAS) AF: 0.919 AC: 4431 AN: 4824

European-Finnish (FIN) AF: 0.964 AC: 10233 AN: 10610

Middle Eastern (MID) AF: 0.912 AC: 268 AN: 294

European-Non Finnish (NFE) AF: 0.947 AC: 64379 AN: 67988

Other (OTH) AF: 0.940 AC: 1988 AN: 2116

Alfa AF: 0.954 Hom.: 8069

Bravo AF: 0.961

Asia WGS AF: 0.960 AC: 3340 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.42
DANN	Benign	0.41
PhyloP100		-1.1
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: rs619686; hg19: chr1-110218761; COSMIC: COSV53981964; COSMIC: COSV53981964;