ENST00000429410.2:n.82+11784A>C

Variant names:

• chr1-109724132-A-C
• rs11101992
• ENST00000429410.2:n.82+11784A>C

Variant summary

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

The ENST00000429410.2(GSTM5):​n.82+11784A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.383 in 152,100 control chromosomes in the GnomAD database, including 14,993 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 0.38 (14993 hom., cov: 32)
• Consequence: GSTM5 ENST00000429410.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.612

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.734 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSTM5	ENST00000429410.2	n.82+11784A>C		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.382 AC: 58102 AN: 151982 Hom.: 14958 Cov.: 32

Gnomad AFR AF: 0.741

Gnomad AMI AF: 0.452

Gnomad AMR AF: 0.278

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.128

Gnomad SAS AF: 0.273

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.247

Gnomad OTH AF: 0.333

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

GnomAD4 genome AF: 0.383 AC: 58189 AN: 152100 Hom.: 14993 Cov.: 32 AF XY: 0.378 AC XY: 28117 AN XY: 74366

Gnomad4 AFR AF: 0.741

Gnomad4 AMR AF: 0.278

Gnomad4 ASJ AF: 0.219

Gnomad4 EAS AF: 0.128

Gnomad4 SAS AF: 0.271

Gnomad4 FIN AF: 0.235

Gnomad4 NFE AF: 0.247

Gnomad4 OTH AF: 0.331

Alfa AF: 0.270 Hom.: 8306

Bravo AF: 0.398

Asia WGS AF: 0.240 AC: 839 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.3
DANN	Benign	0.51

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11101992; hg19: chr1-110266754;