rs17567

Variant summary

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

The NM_001981.3(EPS15):ā€‹c.2466A>Gā€‹(p.Ile822Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 1,613,240 control chromosomes in the GnomAD database, including 46,077 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: š‘“ 0.29 ( 7978 hom., cov: 32)
Exomes š‘“: 0.22 ( 38099 hom. )

Consequence

EPS15
NM_001981.3 missense

Scores

18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.699
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=1.566112E-4).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.515 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
EPS15NM_001981.3 linkuse as main transcriptc.2466A>G p.Ile822Met missense_variant 24/25 ENST00000371733.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
EPS15ENST00000371733.8 linkuse as main transcriptc.2466A>G p.Ile822Met missense_variant 24/251 NM_001981.3 P3P42566-1

Frequencies

GnomAD3 genomes
AF:
0.285
AC:
43282
AN:
151974
Hom.:
7935
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.520
Gnomad AMI
AF:
0.287
Gnomad AMR
AF:
0.189
Gnomad ASJ
AF:
0.217
Gnomad EAS
AF:
0.0114
Gnomad SAS
AF:
0.110
Gnomad FIN
AF:
0.120
Gnomad MID
AF:
0.275
Gnomad NFE
AF:
0.227
Gnomad OTH
AF:
0.250
GnomAD3 exomes
AF:
0.195
AC:
49089
AN:
251336
Hom.:
6458
AF XY:
0.191
AC XY:
25909
AN XY:
135840
show subpopulations
Gnomad AFR exome
AF:
0.528
Gnomad AMR exome
AF:
0.127
Gnomad ASJ exome
AF:
0.211
Gnomad EAS exome
AF:
0.0119
Gnomad SAS exome
AF:
0.123
Gnomad FIN exome
AF:
0.135
Gnomad NFE exome
AF:
0.227
Gnomad OTH exome
AF:
0.208
GnomAD4 exome
AF:
0.217
AC:
317049
AN:
1461148
Hom.:
38099
Cov.:
32
AF XY:
0.214
AC XY:
155617
AN XY:
726908
show subpopulations
Gnomad4 AFR exome
AF:
0.532
Gnomad4 AMR exome
AF:
0.134
Gnomad4 ASJ exome
AF:
0.209
Gnomad4 EAS exome
AF:
0.00741
Gnomad4 SAS exome
AF:
0.124
Gnomad4 FIN exome
AF:
0.137
Gnomad4 NFE exome
AF:
0.229
Gnomad4 OTH exome
AF:
0.221
GnomAD4 genome
AF:
0.285
AC:
43375
AN:
152092
Hom.:
7978
Cov.:
32
AF XY:
0.275
AC XY:
20486
AN XY:
74362
show subpopulations
Gnomad4 AFR
AF:
0.521
Gnomad4 AMR
AF:
0.189
Gnomad4 ASJ
AF:
0.217
Gnomad4 EAS
AF:
0.0112
Gnomad4 SAS
AF:
0.110
Gnomad4 FIN
AF:
0.120
Gnomad4 NFE
AF:
0.227
Gnomad4 OTH
AF:
0.248
Alfa
AF:
0.234
Hom.:
11965
Bravo
AF:
0.303
TwinsUK
AF:
0.220
AC:
815
ALSPAC
AF:
0.229
AC:
883
ESP6500AA
AF:
0.514
AC:
2266
ESP6500EA
AF:
0.230
AC:
1982
ExAC
AF:
0.206
AC:
25064
Asia WGS
AF:
0.102
AC:
357
AN:
3478
EpiCase
AF:
0.229
EpiControl
AF:
0.229

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.055
BayesDel_addAF
Benign
-0.76
T
BayesDel_noAF
Benign
-0.71
CADD
Benign
17
DANN
Benign
0.91
DEOGEN2
Benign
0.0094
T;T
Eigen
Benign
-0.56
Eigen_PC
Benign
-0.29
FATHMM_MKL
Benign
0.18
N
LIST_S2
Benign
0.013
T;T
MetaRNN
Benign
0.00016
T;T
MetaSVM
Benign
-0.95
T
MutationAssessor
Benign
-1.1
.;N
MutationTaster
Benign
1.0
P;P;P
PrimateAI
Benign
0.35
T
PROVEAN
Benign
0.81
N;N
REVEL
Benign
0.086
Sift
Benign
0.22
T;T
Sift4G
Benign
0.16
T;T
Polyphen
0.0010
B;B
Vest4
0.025
MPC
0.13
ClinPred
0.0092
T
GERP RS
5.8
Varity_R
0.040
gMVP
0.036

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

Publications

LitVar

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

Other links and lift over

dbSNP: rs17567; hg19: chr1-51826921; COSMIC: COSV65541248; API