1-109668196-C-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000848.4(GSTM2):​c.36+45C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000837 in 1,194,620 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 29)
  • Exomes 𝑓: 8.4e-7 (0 hom.)
• Consequence: GSTM2 NM_000848.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.51
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSTM2	NM_000848.4	c.36+45C>A		intron_variant	Intron 1 of 7	ENST00000241337.9	NP_000839.1
GSTM2	NM_001142368.2	c.36+45C>A		intron_variant	Intron 1 of 8		NP_001135840.1
GSTM2	XR_007059236.1	n.95+45C>A		intron_variant	Intron 1 of 6
GSTM2	XR_007059237.1	n.95+45C>A		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>A		intron_variant	Intron 1 of 7	1	NM_000848.4	ENSP00000241337.4

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 8.37e-7 AC: 1 AN: 1194620 Hom.: 0 Cov.: 21 AF XY: 0.00000165 AC XY: 1 AN XY: 605840

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 27940

American (AMR) AF: 0.00 AC: 0 AN: 43692

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24172

East Asian (EAS) AF: 0.00 AC: 0 AN: 38254

South Asian (SAS) AF: 0.00 AC: 0 AN: 80884

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49988

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3906

European-Non Finnish (NFE) AF: 0.00000114 AC: 1 AN: 874676

Other (OTH) AF: 0.00 AC: 0 AN: 51108

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.36
DANN	Benign	0.37
PhyloP100		-4.5
PromoterAI		0.27	Neutral
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

Other links and lift over

dbSNP: rs2073483; hg19: chr1-110210818;