chr1-109668196-C-T

Position:

• chr1-109668196-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

GSTM2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
GSTM2	NM_000848.4	c.36+45C>T		intron_variant		ENST00000241337.9	NP_000839.1
GSTM2	NM_001142368.2	c.36+45C>T		intron_variant			NP_001135840.1
GSTM2	XR_007059236.1	n.95+45C>T		intron_variant
GSTM2	XR_007059237.1	n.95+45C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSTM2	ENST00000241337.9	c.36+45C>T		intron_variant		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

GnomAD3 exomes AF: 0.448 AC: 104690 AN: 233524 Hom.: 24717 AF XY: 0.443 AC XY: 56862 AN XY: 128238

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 SAS exome AF: 0.426

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

Gnomad4 AFR exome AF: 0.184

Gnomad4 AMR exome AF: 0.589

Gnomad4 ASJ exome AF: 0.425

Gnomad4 EAS exome AF: 0.710

Gnomad4 SAS exome AF: 0.429

Gnomad4 FIN exome AF: 0.444

Gnomad4 NFE exome AF: 0.416

Gnomad4 OTH exome AF: 0.436

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

Gnomad4 AFR AF: 0.185

Gnomad4 AMR AF: 0.513

Gnomad4 ASJ AF: 0.420

Gnomad4 EAS AF: 0.669

Gnomad4 SAS AF: 0.428

Gnomad4 FIN AF: 0.418

Gnomad4 NFE AF: 0.402

Gnomad4 OTH AF: 0.419

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
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs2073483; hg19: chr1-110210818;