1-109753150-T-C

Variant names:

• chr1-109753150-T-C
• rs1887547
• NM_133181.4:c.1167A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_133181.4(EPS8L3):​c.1167A>G​(p.Ser389Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.631 in 1,612,672 control chromosomes in the GnomAD database, including 326,142 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 0.69 (37610 hom., cov: 31)
  • Exomes 𝑓: 0.62 (288532 hom.)
• Consequence: EPS8L3 NM_133181.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.09
• Publications: 35 publications found

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

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP7: Synonymous conserved (PhyloP=-2.09 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.868 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPS8L3	NM_133181.4	c.1167A>G	p.Ser389Ser	synonymous_variant	Exon 13 of 19	ENST00000361965.9	NP_573444.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPS8L3	ENST00000361965.9	c.1167A>G	p.Ser389Ser	synonymous_variant	Exon 13 of 19	1	NM_133181.4	ENSP00000355255.4

Frequencies

GnomAD3 genomes AF: 0.692 AC: 105021 AN: 151856 Hom.: 37553 Cov.: 31

Gnomad AFR AF: 0.876

Gnomad AMI AF: 0.652

Gnomad AMR AF: 0.641

Gnomad ASJ AF: 0.573

Gnomad EAS AF: 0.838

Gnomad SAS AF: 0.723

Gnomad FIN AF: 0.572

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.604

Gnomad OTH AF: 0.644

GnomAD2 exomes AF: 0.655 AC: 164052 AN: 250510 AF XY: 0.649

Gnomad AFR exome AF: 0.880

Gnomad AMR exome AF: 0.670

Gnomad ASJ exome AF: 0.569

Gnomad EAS exome AF: 0.841

Gnomad FIN exome AF: 0.564

Gnomad NFE exome AF: 0.598

Gnomad OTH exome AF: 0.600

GnomAD4 exome AF: 0.625 AC: 912883 AN: 1460698 Hom.: 288532 Cov.: 46 AF XY: 0.626 AC XY: 455078 AN XY: 726622

African (AFR) AF: 0.883 AC: 29531 AN: 33460

American (AMR) AF: 0.668 AC: 29763 AN: 44578

Ashkenazi Jewish (ASJ) AF: 0.572 AC: 14918 AN: 26078

East Asian (EAS) AF: 0.827 AC: 32811 AN: 39694

South Asian (SAS) AF: 0.715 AC: 61538 AN: 86032

European-Finnish (FIN) AF: 0.564 AC: 30087 AN: 53386

Middle Eastern (MID) AF: 0.583 AC: 3357 AN: 5762

European-Non Finnish (NFE) AF: 0.605 AC: 672428 AN: 1111370

Other (OTH) AF: 0.637 AC: 38450 AN: 60338

GnomAD4 genome AF: 0.692 AC: 105138 AN: 151974 Hom.: 37610 Cov.: 31 AF XY: 0.690 AC XY: 51211 AN XY: 74256

African (AFR) AF: 0.876 AC: 36320 AN: 41460

American (AMR) AF: 0.642 AC: 9804 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.573 AC: 1987 AN: 3468

East Asian (EAS) AF: 0.837 AC: 4300 AN: 5138

South Asian (SAS) AF: 0.723 AC: 3471 AN: 4804

European-Finnish (FIN) AF: 0.572 AC: 6036 AN: 10550

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.605 AC: 41083 AN: 67958

Other (OTH) AF: 0.647 AC: 1366 AN: 2112

Alfa AF: 0.628 Hom.: 64349

Bravo AF: 0.703

Asia WGS AF: 0.755 AC: 2627 AN: 3478

EpiCase AF: 0.591

EpiControl AF: 0.583

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.20
DANN	Benign	0.35
PhyloP100		-2.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1887547; hg19: chr1-110295772; COSMIC: COSV62609493; COSMIC: COSV62609493;