dbSNP rs2274536: EPS8L3:c.1434+40T>C (chr1-109751955-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_133181.4(EPS8L3):c.1434+40T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 1,565,574 control chromosomes in the GnomAD database, including 79,918 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 0.38 ( 12615 hom., cov: 31)

Exomes 𝑓: 0.30 ( 67303 hom. )

Consequence

EPS8L3
NM_133181.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.368

Variant links:

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]

EPS8L3 links:

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]

GSTM5 links:

ENSG00000241720 (HGNC:):

ENSG00000241720 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.602 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPS8L3	NM_133181.4 link	c.1434+40T>C		intron_variant	Intron 15 of 18	ENST00000361965.9	NP_573444.2	Q8TE67-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPS8L3	ENST00000361965.9 link	c.1434+40T>C		intron_variant	Intron 15 of 18	1	NM_133181.4	ENSP00000355255.4		Q8TE67-1

Frequencies

GnomAD3 genomes

AF:

0.378

AC:

57399

AN:

151740

Hom.:

12586

Cov.:

show subpopulations

Gnomad AFR

AF:

0.608

Gnomad AMI

AF:

0.483

Gnomad AMR

AF:

0.286

Gnomad ASJ

AF:

0.331

Gnomad EAS

AF:

0.109

Gnomad SAS

AF:

0.293

Gnomad FIN

AF:

0.285

Gnomad MID

AF:

0.342

Gnomad NFE

AF:

0.303

Gnomad OTH

AF:

0.333

GnomAD3 exomes

AF:

0.296

AC:

63577

AN:

214480

Hom.:

10811

AF XY:

0.291

AC XY:

33184

AN XY:

113902

show subpopulations

Gnomad AFR exome

AF:

0.619

Gnomad AMR exome

AF:

0.222

Gnomad ASJ exome

AF:

0.321

Gnomad EAS exome

AF:

0.102

Gnomad SAS exome

AF:

0.301

Gnomad FIN exome

AF:

0.278

Gnomad NFE exome

AF:

0.304

Gnomad OTH exome

AF:

0.285

GnomAD4 exome

AF:

0.301

AC:

425811

AN:

1413716

Hom.:

67303

Cov.:

AF XY:

0.300

AC XY:

209501

AN XY:

697630

show subpopulations

Gnomad4 AFR exome

AF:

0.617

Gnomad4 AMR exome

AF:

0.231

Gnomad4 ASJ exome

AF:

0.334

Gnomad4 EAS exome

AF:

0.116

Gnomad4 SAS exome

AF:

0.295

Gnomad4 FIN exome

AF:

0.273

Gnomad4 NFE exome

AF:

0.302

Gnomad4 OTH exome

AF:

0.309

GnomAD4 genome

AF:

0.378

AC:

57478

AN:

151858

Hom.:

12615

Cov.:

AF XY:

0.372

AC XY:

27636

AN XY:

74232

show subpopulations

Gnomad4 AFR

AF:

0.608

Gnomad4 AMR

AF:

0.287

Gnomad4 ASJ

AF:

0.331

Gnomad4 EAS

AF:

0.109

Gnomad4 SAS

AF:

0.291

Gnomad4 FIN

AF:

0.285

Gnomad4 NFE

AF:

0.303

Gnomad4 OTH

AF:

0.332

Alfa

AF:

0.310

Hom.:

10662

Bravo

AF:

0.386

Asia WGS

AF:

0.227

AC:

791

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

2.2

DANN

Benign

0.68

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over