Variant 1-51356744-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_001981.3(EPS15):c.2647G>C(p.Glu883Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000923 in 1,613,910 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000095 ( 0 hom. )

Consequence

EPS15
NM_001981.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.99

Variant links:

Genes affected

EPS15 (HGNC:3419): (epidermal growth factor receptor pathway substrate 15) This gene encodes a protein that is part of the EGFR pathway. The protein is present at clatherin-coated pits and is involved in receptor-mediated endocytosis of EGF. Notably, this gene is rearranged with the HRX/ALL/MLL gene in acute myelogeneous leukemias. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, May 2009]

EPS15 links:

EPS15 (HGNC:):

EPS15 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.40230867).

BS2

High AC in GnomAd4 at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPS15	NM_001981.3 linkuse as main transcript	c.2647G>C	p.Glu883Gln	missense_variant	25/25	ENST00000371733.8	NP_001972.1	P42566-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPS15	ENST00000371733.8 linkuse as main transcript	c.2647G>C	p.Glu883Gln	missense_variant	25/25	1	NM_001981.3	ENSP00000360798.3		P42566-1

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000211

AC:

AN:

251268

Hom.:

AF XY:

0.000184

AC XY:

AN XY:

135820

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000323

Gnomad NFE exome

AF:

0.000405

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000951

AC:

139

AN:

1461726

Hom.:

Cov.:

AF XY:

0.0000825

AC XY:

AN XY:

727172

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000356

Gnomad4 NFE exome

AF:

0.000103

Gnomad4 OTH exome

AF:

0.0000994

GnomAD4 genome

AF:

0.0000657

AC:

AN:

152184

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000102

Hom.:

Bravo

AF:

0.0000604

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000379

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 29, 2024

The c.2647G>C (p.E883Q) alteration is located in exon 25 (coding exon 25) of the EPS15 gene. This alteration results from a G to C substitution at nucleotide position 2647, causing the glutamic acid (E) at amino acid position 883 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.56

BayesDel_addAF

Benign

-0.092

BayesDel_noAF

Uncertain

-0.050

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

T;T

Eigen

Pathogenic

0.87

Eigen_PC

Pathogenic

0.86

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.98

D;D

M_CAP

Benign

0.029

MetaRNN

Benign

0.40

T;T

MetaSVM

Uncertain

-0.27

MutationAssessor

Uncertain

2.5

.;M

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-1.9

N;N

REVEL

Benign

0.20

Sift

Pathogenic

0.0

D;D

Sift4G

Uncertain

0.0060

D;D

Polyphen

1.0

D;D

Vest4

0.60

MVP

0.80

MPC

0.58

ClinPred

0.33

GERP RS

5.9

Varity_R

0.30

gMVP

0.38

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