1-109691664-A-G

Position:

• chr1-109691664-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000561.4(GSTM1):​c.567+1100A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.17 (5280 hom., cov: 12)
• Consequence: GSTM1 NM_000561.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.40

Genes affected

GSTM1 (HGNC:4632): (glutathione S-transferase mu 1) 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. Null mutations of this class mu gene have been linked with an increase in a number of cancers, likely due to an increased susceptibility to environmental toxins and carcinogens. Multiple protein isoforms are encoded by transcript variants of this gene. [provided by RefSeq, Jul 2008]

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]

GSTM1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.309 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GSTM1	NM_000561.4	c.567+1100A>G		intron_variant		ENST00000309851.10	NP_000552.2
GSTM1	NM_146421.3	c.456+1298A>G		intron_variant			NP_666533.1
GSTM1	XM_005270782.6	c.465+1100A>G		intron_variant			XP_005270839.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSTM1	ENST00000309851.10	c.567+1100A>G		intron_variant		1	NM_000561.4	ENSP00000311469.5

Frequencies

GnomAD3 genomes AF: 0.165 AC: 13339 AN: 80812 Hom.: 5272 Cov.: 12

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.0349

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.0798

Gnomad EAS AF: 0.328

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.0490

Gnomad MID AF: 0.107

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.156

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.165 AC: 13361 AN: 80924 Hom.: 5280 Cov.: 12 AF XY: 0.165 AC XY: 6501 AN XY: 39458

Gnomad4 AFR AF: 0.199

Gnomad4 AMR AF: 0.283

Gnomad4 ASJ AF: 0.0798

Gnomad4 EAS AF: 0.326

Gnomad4 SAS AF: 0.327

Gnomad4 FIN AF: 0.0490

Gnomad4 NFE AF: 0.107

Gnomad4 OTH AF: 0.155

Alfa AF: 0.0358 Hom.: 0

Asia WGS AF: 0.321 AC: 609 AN: 1908

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.027
DANN	Benign	0.46

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs2239892; hg19: chr1-110234286;