rs11101996

Positions:

• chr1-109728085-T-C

Variant summary

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

The ENST00000431955.1(ENSG00000241720):​n.249+2017T>C variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 152,088 control chromosomes in the GnomAD database, including 15,681 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 0.44 (15681 hom., cov: 33)
• Consequence: ENST00000431955.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.05

Genes affected

(HGNC:):

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=-1.05).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.718 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000431955.1	n.249+2017T>C		intron_variant, non_coding_transcript_variant		3
GSTM5	ENST00000429410.2	n.82+15737T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.445 AC: 67569 AN: 151970 Hom.: 15660 Cov.: 33

Gnomad AFR AF: 0.522

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.442

Gnomad ASJ AF: 0.430

Gnomad EAS AF: 0.738

Gnomad SAS AF: 0.465

Gnomad FIN AF: 0.383

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.388

Gnomad OTH AF: 0.438

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

GnomAD4 genome AF: 0.445 AC: 67631 AN: 152088 Hom.: 15681 Cov.: 33 AF XY: 0.444 AC XY: 33009 AN XY: 74342

Gnomad4 AFR AF: 0.522

Gnomad4 AMR AF: 0.442

Gnomad4 ASJ AF: 0.430

Gnomad4 EAS AF: 0.738

Gnomad4 SAS AF: 0.465

Gnomad4 FIN AF: 0.383

Gnomad4 NFE AF: 0.388

Gnomad4 OTH AF: 0.442

Alfa AF: 0.421 Hom.: 1714

Bravo AF: 0.452

Asia WGS AF: 0.550 AC: 1911 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.15
DANN	Benign	0.21

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11101996; hg19: chr1-110270707;