1-109733122-A-G

Variant names:

• chr1-109733122-A-G
• rs1927328
• ENST00000429410.2:n.82+20774A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000429410.2(GSTM5):​n.82+20774A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 152,134 control chromosomes in the GnomAD database, including 7,173 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 (7173 hom., cov: 32)
• Consequence: GSTM5 ENST00000429410.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.20
• Publications: 22 publications found

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]

ENSG00000241720 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.728 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+20774A>G		intron_variant	Intron 1 of 1	2
ENSG00000241720	ENST00000431955.1	n.425+772A>G		intron_variant	Intron 2 of 3	3

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41737 AN: 152016 Hom.: 7165 Cov.: 32

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.180

Gnomad AMR AF: 0.345

Gnomad ASJ AF: 0.320

Gnomad EAS AF: 0.748

Gnomad SAS AF: 0.428

Gnomad FIN AF: 0.312

Gnomad MID AF: 0.287

Gnomad NFE AF: 0.307

Gnomad OTH AF: 0.284

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

GnomAD4 genome AF: 0.275 AC: 41772 AN: 152134 Hom.: 7173 Cov.: 32 AF XY: 0.278 AC XY: 20692 AN XY: 74352

African (AFR) AF: 0.106 AC: 4417 AN: 41538

American (AMR) AF: 0.345 AC: 5268 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.320 AC: 1110 AN: 3470

East Asian (EAS) AF: 0.747 AC: 3870 AN: 5178

South Asian (SAS) AF: 0.430 AC: 2063 AN: 4800

European-Finnish (FIN) AF: 0.312 AC: 3298 AN: 10582

Middle Eastern (MID) AF: 0.291 AC: 85 AN: 292

European-Non Finnish (NFE) AF: 0.307 AC: 20888 AN: 67974

Other (OTH) AF: 0.289 AC: 609 AN: 2110

Alfa AF: 0.300 Hom.: 12047

Bravo AF: 0.270

Asia WGS AF: 0.511 AC: 1776 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	8.0
DANN	Benign	0.78
PhyloP100		1.2

Splicing

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

Other links and lift over

dbSNP: rs1927328; hg19: chr1-110275744; COSMIC: COSV56661875;