1-109750234-G-C

Variant names:

• chr1-109750234-G-C
• rs15864
• NM_133181.4:c.*157C>G

Variant summary

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

The NM_133181.4(EPS8L3):​c.*157C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 841,270 control chromosomes in the GnomAD database, including 47,647 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 0.26 (6683 hom., cov: 32)
  • Exomes 𝑓: 0.33 (40964 hom.)
• Consequence: EPS8L3 NM_133181.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.85

Genes affected

EPS8L3 (HGNC:21297): (EPS8 signaling adaptor L3) This gene encodes a protein that is related to epidermal growth factor receptor pathway substrate 8 (EPS8), a substrate for the epidermal growth factor receptor. The function of this protein is unknown. Alternatively spliced transcript variants encoding different isoforms exist. [provided by RefSeq, Jul 2008]

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

Verdict is Benign. Variant got -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 = 0.72 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPS8L3	NM_133181.4	c.*157C>G		3_prime_UTR_variant	Exon 19 of 19	ENST00000361965.9	NP_573444.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPS8L3	ENST00000361965	c.*157C>G		3_prime_UTR_variant	Exon 19 of 19	1	NM_133181.4	ENSP00000355255.4

Frequencies

GnomAD3 genomes AF: 0.256 AC: 38927 AN: 151944 Hom.: 6683 Cov.: 32

Gnomad AFR AF: 0.0651

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.335

Gnomad ASJ AF: 0.290

Gnomad EAS AF: 0.741

Gnomad SAS AF: 0.393

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.303

Gnomad OTH AF: 0.271

GnomAD4 exome AF: 0.327 AC: 225256 AN: 689208 Hom.: 40964 Cov.: 9 AF XY: 0.331 AC XY: 117454 AN XY: 355348

Gnomad4 AFR exome AF: 0.0568

Gnomad4 AMR exome AF: 0.413

Gnomad4 ASJ exome AF: 0.287

Gnomad4 EAS exome AF: 0.718

Gnomad4 SAS exome AF: 0.395

Gnomad4 FIN exome AF: 0.290

Gnomad4 NFE exome AF: 0.303

Gnomad4 OTH exome AF: 0.317

GnomAD4 genome AF: 0.256 AC: 38932 AN: 152062 Hom.: 6683 Cov.: 32 AF XY: 0.261 AC XY: 19368 AN XY: 74334

Gnomad4 AFR AF: 0.0650

Gnomad4 AMR AF: 0.334

Gnomad4 ASJ AF: 0.290

Gnomad4 EAS AF: 0.740

Gnomad4 SAS AF: 0.394

Gnomad4 FIN AF: 0.288

Gnomad4 NFE AF: 0.303

Gnomad4 OTH AF: 0.275

Alfa AF: 0.267 Hom.: 795

Bravo AF: 0.252

Asia WGS AF: 0.493 AC: 1712 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	0.013
DANN	Benign	0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs15864; hg19: chr1-110292856; COSMIC: COSV62609033; COSMIC: COSV62609033;