rs4970774

Variant names:

• chr1-109726206-A-C
• rs4970774
• ENST00000429410.2:n.82+13858A>C

Your query was ambiguous. Multiple possible variants found:

• chr1-109726206-A-C
• chr1-109726206-A-G
• chr1-109726206-A-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+13858A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.497 in 152,106 control chromosomes in the GnomAD database, including 19,246 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 0.50 (19246 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GSTM5 ENST00000429410.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.32
• Publications: 18 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.708 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

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

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSTM5	ENST00000429410.2	TSL:2	n.82+13858A>C		intron	N/A
	ENSG00000241720	ENST00000431955.1	TSL:3	n.249+138A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.497 AC: 75558 AN: 151988 Hom.: 19219 Cov.: 33

Gnomad AFR AF: 0.553

Gnomad AMI AF: 0.357

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.459

Gnomad EAS AF: 0.728

Gnomad SAS AF: 0.500

Gnomad FIN AF: 0.444

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.492

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.497 AC: 75628 AN: 152106 Hom.: 19246 Cov.: 33 AF XY: 0.496 AC XY: 36888 AN XY: 74352

African (AFR) AF: 0.554 AC: 22963 AN: 41486

American (AMR) AF: 0.489 AC: 7468 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.459 AC: 1594 AN: 3470

East Asian (EAS) AF: 0.727 AC: 3769 AN: 5184

South Asian (SAS) AF: 0.500 AC: 2403 AN: 4808

European-Finnish (FIN) AF: 0.444 AC: 4694 AN: 10576

Middle Eastern (MID) AF: 0.531 AC: 156 AN: 294

European-Non Finnish (NFE) AF: 0.459 AC: 31209 AN: 67984

Other (OTH) AF: 0.496 AC: 1046 AN: 2110

Alfa AF: 0.471 Hom.: 70195

Bravo AF: 0.503

Asia WGS AF: 0.566 AC: 1966 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.28
DANN	Benign	0.50
PhyloP100		-3.3

Splicing

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

Other links and lift over

dbSNP: rs4970774; hg19: chr1-110268828;