1-109726566-C-T

Variant names:

• chr1-109726566-C-T
• rs11101993
• ENST00000429410.2:n.82+14218C>T

Variant summary

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

The ENST00000429410.2(GSTM5):​n.82+14218C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0584 in 152,286 control chromosomes in the GnomAD database, including 388 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 0.058 (388 hom., cov: 33)
• Consequence: GSTM5 ENST00000429410.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.145
• Publications: 5 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000429410.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSTM5	ENST00000429410.2	TSL:2	n.82+14218C>T		intron	N/A
	ENSG00000241720	ENST00000431955.1	TSL:3	n.249+498C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0584 AC: 8883 AN: 152168 Hom.: 383 Cov.: 33

Gnomad AFR AF: 0.0139

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.0916

Gnomad ASJ AF: 0.0328

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.0442

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0707

Gnomad OTH AF: 0.0580

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

GnomAD4 genome AF: 0.0584 AC: 8897 AN: 152286 Hom.: 388 Cov.: 33 AF XY: 0.0591 AC XY: 4399 AN XY: 74452

African (AFR) AF: 0.0139 AC: 577 AN: 41562

American (AMR) AF: 0.0925 AC: 1416 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0328 AC: 114 AN: 3472

East Asian (EAS) AF: 0.129 AC: 669 AN: 5178

South Asian (SAS) AF: 0.122 AC: 590 AN: 4826

European-Finnish (FIN) AF: 0.0442 AC: 469 AN: 10608

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0707 AC: 4812 AN: 68026

Other (OTH) AF: 0.0583 AC: 123 AN: 2108

Alfa AF: 0.0565 Hom.: 93

Bravo AF: 0.0594

Asia WGS AF: 0.130 AC: 451 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.3
DANN	Benign	0.48
PhyloP100		0.14

Splicing

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

Other links and lift over

dbSNP: rs11101993; hg19: chr1-110269188;