chr1-109670836-T-C

Position:

• chr1-109670836-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
GSTM2	NM_000848.4	c.361-451T>C		intron_variant		ENST00000241337.9	NP_000839.1
GSTM2	NM_001142368.2	c.361-451T>C		intron_variant			NP_001135840.1
GSTM2	XR_007059236.1	n.923-451T>C		intron_variant, non_coding_transcript_variant
GSTM2	XR_007059237.1	n.947-451T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSTM2	ENST00000241337.9	c.361-451T>C		intron_variant		1	NM_000848.4	ENSP00000241337	P1

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

Gnomad4 AFR exome AF: 0.976

Gnomad4 AMR exome AF: 0.946

Gnomad4 ASJ exome AF: 0.870

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.886

Gnomad4 FIN exome AF: 0.929

Gnomad4 NFE exome AF: 0.938

Gnomad4 OTH exome AF: 0.928

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

Gnomad4 AFR AF: 0.976

Gnomad4 AMR AF: 0.947

Gnomad4 ASJ AF: 0.924

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.919

Gnomad4 FIN AF: 0.962

Gnomad4 NFE AF: 0.947

Gnomad4 OTH AF: 0.939

Alfa AF: 0.944 Hom.: 97389

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
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		0.95

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

Publications

LitVar

Other links and lift over

dbSNP: rs673151; hg19: chr1-110213458; COSMIC: COSV53981947; COSMIC: COSV53981947;