12-15623161-C-T

Position:

chr12-15623161-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_004447.6(EPS8):c.2352G>A(p.Leu784=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0487 in 1,604,462 control chromosomes in the GnomAD database, including 10,231 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 5081 hom., cov: 32)

Exomes 𝑓: 0.038 ( 5150 hom. )

Consequence

EPS8
NM_004447.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.489

Variant links:

Genes affected

EPS8 (HGNC:3420): (EGFR pathway substrate 8, signaling adaptor) This gene encodes a member of the EPS8 family. This protein contains one PH domain and one SH3 domain. It functions as part of the EGFR pathway, though its exact role has not been determined. Highly similar proteins in other organisms are involved in the transduction of signals from Ras to Rac and growth factor-mediated actin remodeling. Alternate transcriptional splice variants of this gene have been observed but have not been thoroughly characterized. [provided by RefSeq, Jul 2008]

EPS8 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant 12-15623161-C-T is Benign according to our data. Variant chr12-15623161-C-T is described in ClinVar as [Benign]. Clinvar id is 508137.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.489 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.48 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPS8	NM_004447.6 linkuse as main transcript	c.2352G>A	p.Leu784=	synonymous_variant	20/21	ENST00000281172.10	NP_004438.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPS8	ENST00000281172.10 linkuse as main transcript	c.2352G>A	p.Leu784=	synonymous_variant	20/21	1	NM_004447.6	ENSP00000281172	P1	Q12929-1

Frequencies

GnomAD3 genomes

AF:

0.154

AC:

23361

AN:

151970

Hom.:

5072

Cov.:

show subpopulations

Gnomad AFR

AF:

0.485

Gnomad AMI

AF:

0.0132

Gnomad AMR

AF:

0.0655

Gnomad ASJ

AF:

0.0196

Gnomad EAS

AF:

0.0415

Gnomad SAS

AF:

0.0459

Gnomad FIN

AF:

0.00245

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.0222

Gnomad OTH

AF:

0.115

GnomAD3 exomes

AF:

0.0578

AC:

13963

AN:

241568

Hom.:

2125

AF XY:

0.0493

AC XY:

6430

AN XY:

130322

show subpopulations

Gnomad AFR exome

AF:

0.495

Gnomad AMR exome

AF:

0.0316

Gnomad ASJ exome

AF:

0.0244

Gnomad EAS exome

AF:

0.0433

Gnomad SAS exome

AF:

0.0440

Gnomad FIN exome

AF:

0.00397

Gnomad NFE exome

AF:

0.0223

Gnomad OTH exome

AF:

0.0355

GnomAD4 exome

AF:

0.0376

AC:

54669

AN:

1452376

Hom.:

5150

Cov.:

AF XY:

0.0360

AC XY:

26017

AN XY:

722048

show subpopulations

Gnomad4 AFR exome

AF:

0.512

Gnomad4 AMR exome

AF:

0.0352

Gnomad4 ASJ exome

AF:

0.0238

Gnomad4 EAS exome

AF:

0.0354

Gnomad4 SAS exome

AF:

0.0452

Gnomad4 FIN exome

AF:

0.00503

Gnomad4 NFE exome

AF:

0.0241

Gnomad4 OTH exome

AF:

0.0534

GnomAD4 genome

AF:

0.154

AC:

23404

AN:

152086

Hom.:

5081

Cov.:

AF XY:

0.148

AC XY:

11020

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.485

Gnomad4 AMR

AF:

0.0652

Gnomad4 ASJ

AF:

0.0196

Gnomad4 EAS

AF:

0.0414

Gnomad4 SAS

AF:

0.0458

Gnomad4 FIN

AF:

0.00245

Gnomad4 NFE

AF:

0.0222

Gnomad4 OTH

AF:

0.114

Alfa

AF:

0.0708

Hom.:

1206

Bravo

AF:

0.173

Asia WGS

AF:

0.0640

AC:

225

AN:

3478

EpiCase

AF:

0.0243

EpiControl

AF:

0.0256

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	May 24, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Aug 23, 2017	p.Leu784Leu in exon 20 of EPS8: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue, is not located withi n the splice consensus sequence, and has been identified in 48.80% (5077/10404) of African chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.br oadinstitute.org; dbSNP rs1126786). -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 09, 2017	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

3.7

DANN

Benign

0.69

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over