chr1-109712552-T-G

Position:

• chr1-109712552-T-G

Variant summary

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

The NM_000851.4(GSTM5):​c.37-66T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.298 in 1,569,484 control chromosomes in the GnomAD database, including 76,320 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 0.27 (6501 hom., cov: 32)
  • Exomes 𝑓: 0.30 (69819 hom.)
• Consequence: GSTM5 NM_000851.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.578

Genes affected

GSTM5 (HGNC:4637): (glutathione S-transferase mu 5) 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. Diversification of these genes has occurred in regions encoding substrate-binding domains, as well as in tissue expression patterns, to accommodate an increasing number of foreign compounds. [provided by RefSeq, Jul 2008]

GSTM5 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.675 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GSTM5	NM_000851.4	c.37-66T>G		intron_variant		ENST00000256593.8	NP_000842.2
GSTM5	XM_005270784.5	c.37-66T>G		intron_variant			XP_005270841.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSTM5	ENST00000256593.8	c.37-66T>G		intron_variant		1	NM_000851.4	ENSP00000256593.3

Frequencies

GnomAD3 genomes AF: 0.268 AC: 40641 AN: 151748 Hom.: 6494 Cov.: 32

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.365

Gnomad ASJ AF: 0.272

Gnomad EAS AF: 0.695

Gnomad SAS AF: 0.340

Gnomad FIN AF: 0.311

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.271

GnomAD4 exome AF: 0.302 AC: 427665 AN: 1417622 Hom.: 69819 Cov.: 28 AF XY: 0.302 AC XY: 214125 AN XY: 707882

Gnomad4 AFR exome AF: 0.125

Gnomad4 AMR exome AF: 0.472

Gnomad4 ASJ exome AF: 0.271

Gnomad4 EAS exome AF: 0.689

Gnomad4 SAS exome AF: 0.346

Gnomad4 FIN exome AF: 0.319

Gnomad4 NFE exome AF: 0.282

Gnomad4 OTH exome AF: 0.303

GnomAD4 genome AF: 0.268 AC: 40665 AN: 151862 Hom.: 6501 Cov.: 32 AF XY: 0.273 AC XY: 20225 AN XY: 74214

Gnomad4 AFR AF: 0.136

Gnomad4 AMR AF: 0.365

Gnomad4 ASJ AF: 0.272

Gnomad4 EAS AF: 0.694

Gnomad4 SAS AF: 0.341

Gnomad4 FIN AF: 0.311

Gnomad4 NFE AF: 0.283

Gnomad4 OTH AF: 0.278

Alfa AF: 0.281 Hom.: 3587

Bravo AF: 0.268

Asia WGS AF: 0.466 AC: 1619 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.9
DANN	Benign	0.42

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: rs929166; hg19: chr1-110255174;