1-109670836-T-C

Variant names:

• chr1-109670836-T-C
• rs673151
• NM_000848.4:c.361-451T>C

Variant summary

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

The NM_000848.4(GSTM2):​c.361-451T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.956 in 156,352 control chromosomes in the GnomAD database, including 71,458 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 (69691 hom., cov: 32)
  • Exomes 𝑓: 0.94 (1767 hom.)
• Consequence: GSTM2 NM_000848.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39
• Publications: 10 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSTM2	NM_000848.4	c.361-451T>C		intron_variant	Intron 5 of 7	ENST00000241337.9	NP_000839.1
GSTM2	NM_001142368.2	c.361-451T>C		intron_variant	Intron 5 of 8		NP_001135840.1
GSTM2	XR_007059236.1	n.923-451T>C		intron_variant	Intron 6 of 6
GSTM2	XR_007059237.1	n.947-451T>C		intron_variant	Intron 6 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSTM2	ENST00000241337.9	c.361-451T>C		intron_variant	Intron 5 of 7	1	NM_000848.4	ENSP00000241337.4

Frequencies

GnomAD3 genomes AF: 0.956 AC: 145540 AN: 152208 Hom.: 69628 Cov.: 32

Gnomad AFR AF: 0.976

Gnomad AMI AF: 0.966

Gnomad AMR AF: 0.947

Gnomad ASJ AF: 0.924

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.920

Gnomad FIN AF: 0.962

Gnomad MID AF: 0.902

Gnomad NFE AF: 0.947

Gnomad OTH AF: 0.939

GnomAD4 exome AF: 0.936 AC: 3770 AN: 4026 Hom.: 1767 Cov.: 0 AF XY: 0.936 AC XY: 1995 AN XY: 2132

African (AFR) AF: 0.976 AC: 80 AN: 82

American (AMR) AF: 0.946 AC: 672 AN: 710

Ashkenazi Jewish (ASJ) AF: 0.870 AC: 47 AN: 54

East Asian (EAS) AF: 1.00 AC: 120 AN: 120

South Asian (SAS) AF: 0.886 AC: 273 AN: 308

European-Finnish (FIN) AF: 0.929 AC: 52 AN: 56

Middle Eastern (MID) AF: 1.00 AC: 4 AN: 4

European-Non Finnish (NFE) AF: 0.938 AC: 2342 AN: 2498

Other (OTH) AF: 0.928 AC: 180 AN: 194

GnomAD4 genome AF: 0.956 AC: 145664 AN: 152326 Hom.: 69691 Cov.: 32 AF XY: 0.957 AC XY: 71240 AN XY: 74478

African (AFR) AF: 0.976 AC: 40586 AN: 41574

American (AMR) AF: 0.947 AC: 14491 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.924 AC: 3209 AN: 3472

East Asian (EAS) AF: 0.998 AC: 5177 AN: 5186

South Asian (SAS) AF: 0.919 AC: 4443 AN: 4832

European-Finnish (FIN) AF: 0.962 AC: 10209 AN: 10610

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

European-Non Finnish (NFE) AF: 0.947 AC: 64414 AN: 68036

Other (OTH) AF: 0.939 AC: 1986 AN: 2114

Alfa AF: 0.945 Hom.: 120233

Bravo AF: 0.958

Asia WGS AF: 0.962 AC: 3344 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.62
DANN	Benign	0.59
PhyloP100		-1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		0.95
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: rs673151; hg19: chr1-110213458; COSMIC: COSV53981947; COSMIC: COSV53981947;