1-109668196-C-T

Variant names:

• chr1-109668196-C-T
• rs2073483
• NM_000848.4:c.36+45C>T

Variant summary

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

The NM_000848.4(GSTM2):​c.36+45C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 1,340,168 control chromosomes in the GnomAD database, including 121,619 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 0.37 (11030 hom., cov: 29)
  • Exomes 𝑓: 0.43 (110589 hom.)
• Consequence: GSTM2 NM_000848.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.51
• Publications: 7 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.65 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSTM2	NM_000848.4	c.36+45C>T		intron_variant	Intron 1 of 7	ENST00000241337.9	NP_000839.1
GSTM2	NM_001142368.2	c.36+45C>T		intron_variant	Intron 1 of 8		NP_001135840.1
GSTM2	XR_007059236.1	n.95+45C>T		intron_variant	Intron 1 of 6
GSTM2	XR_007059237.1	n.95+45C>T		intron_variant	Intron 1 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSTM2	ENST00000241337.9	c.36+45C>T		intron_variant	Intron 1 of 7	1	NM_000848.4	ENSP00000241337.4

Frequencies

GnomAD3 genomes AF: 0.365 AC: 54483 AN: 149094 Hom.: 11023 Cov.: 29

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.307

Gnomad AMR AF: 0.513

Gnomad ASJ AF: 0.420

Gnomad EAS AF: 0.669

Gnomad SAS AF: 0.428

Gnomad FIN AF: 0.418

Gnomad MID AF: 0.455

Gnomad NFE AF: 0.402

Gnomad OTH AF: 0.416

GnomAD2 exomes AF: 0.448 AC: 104690 AN: 233524 AF XY: 0.443

Gnomad AFR exome AF: 0.183

Gnomad AMR exome AF: 0.597

Gnomad ASJ exome AF: 0.422

Gnomad EAS exome AF: 0.684

Gnomad FIN exome AF: 0.429

Gnomad NFE exome AF: 0.408

Gnomad OTH exome AF: 0.443

GnomAD4 exome AF: 0.430 AC: 511991 AN: 1190966 Hom.: 110589 Cov.: 21 AF XY: 0.430 AC XY: 259613 AN XY: 604164

African (AFR) AF: 0.184 AC: 5147 AN: 27912

American (AMR) AF: 0.589 AC: 25745 AN: 43682

Ashkenazi Jewish (ASJ) AF: 0.425 AC: 10261 AN: 24152

East Asian (EAS) AF: 0.710 AC: 27132 AN: 38226

South Asian (SAS) AF: 0.429 AC: 34629 AN: 80772

European-Finnish (FIN) AF: 0.444 AC: 22183 AN: 49958

Middle Eastern (MID) AF: 0.504 AC: 1966 AN: 3898

European-Non Finnish (NFE) AF: 0.416 AC: 362709 AN: 871362

Other (OTH) AF: 0.436 AC: 22219 AN: 51004

GnomAD4 genome AF: 0.365 AC: 54500 AN: 149202 Hom.: 11030 Cov.: 29 AF XY: 0.369 AC XY: 26908 AN XY: 72840

African (AFR) AF: 0.185 AC: 7461 AN: 40416

American (AMR) AF: 0.513 AC: 7733 AN: 15064

Ashkenazi Jewish (ASJ) AF: 0.420 AC: 1447 AN: 3448

East Asian (EAS) AF: 0.669 AC: 3350 AN: 5006

South Asian (SAS) AF: 0.428 AC: 1990 AN: 4650

European-Finnish (FIN) AF: 0.418 AC: 4245 AN: 10160

Middle Eastern (MID) AF: 0.462 AC: 135 AN: 292

European-Non Finnish (NFE) AF: 0.402 AC: 26996 AN: 67196

Other (OTH) AF: 0.419 AC: 868 AN: 2074

Alfa AF: 0.311 Hom.: 1365

Bravo AF: 0.367

Asia WGS AF: 0.524 AC: 1815 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.51
DANN	Benign	0.76
PhyloP100		-4.5
PromoterAI		0.12	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs2073483; hg19: chr1-110210818;