Variant rs118081497 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_003566.4(EEA1):c.3216T>A(p.Asn1072Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00261 in 1,612,704 control chromosomes in the GnomAD database, including 114 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0036 ( 11 hom., cov: 32)

Exomes 𝑓: 0.0025 ( 103 hom. )

Consequence

EEA1
NM_003566.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.438

Variant links:

Genes affected

EEA1 (HGNC:3185): (early endosome antigen 1) Enables 1-phosphatidylinositol binding activity; GTP-dependent protein binding activity; and protein homodimerization activity. Involved in endocytosis; vesicle fusion; and viral RNA genome replication. Located in cytosol and early endosome. Is extrinsic component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

EEA1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002201885).

BP6

Variant 12-92782070-A-T is Benign according to our data. Variant chr12-92782070-A-T is described in ClinVar as [Benign]. Clinvar id is 402817.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.058 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EEA1	NM_003566.4 linkuse as main transcript	c.3216T>A	p.Asn1072Lys	missense_variant	23/29	ENST00000322349.13
EEA1	XM_011538814.3 linkuse as main transcript	c.3342T>A	p.Asn1114Lys	missense_variant	24/30

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EEA1	ENST00000322349.13 linkuse as main transcript	c.3216T>A	p.Asn1072Lys	missense_variant	23/29	1	NM_003566.4	P1

Frequencies

GnomAD3 genomes

AF:

0.00363

AC:

552

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000869

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0240

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0229

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.00719

GnomAD3 exomes

AF:

0.0110

AC:

2768

AN:

250662

Hom.:

AF XY:

0.00839

AC XY:

1136

AN XY:

135454

show subpopulations

Gnomad AFR exome

AF:

0.000985

Gnomad AMR exome

AF:

0.0656

Gnomad ASJ exome

AF:

0.0000994

Gnomad EAS exome

AF:

0.0233

Gnomad SAS exome

AF:

0.000392

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.0000971

Gnomad OTH exome

AF:

0.00688

GnomAD4 exome

AF:

0.00251

AC:

3667

AN:

1460456

Hom.:

103

Cov.:

AF XY:

0.00215

AC XY:

1562

AN XY:

726544

show subpopulations

Gnomad4 AFR exome

AF:

0.000448

Gnomad4 AMR exome

AF:

0.0599

Gnomad4 ASJ exome

AF:

0.000153

Gnomad4 EAS exome

AF:

0.0176

Gnomad4 SAS exome

AF:

0.000383

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.0000477

Gnomad4 OTH exome

AF:

0.00320

GnomAD4 genome

AF:

0.00361

AC:

550

AN:

152248

Hom.:

Cov.:

AF XY:

0.00380

AC XY:

283

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.000866

Gnomad4 AMR

AF:

0.0239

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0227

Gnomad4 SAS

AF:

0.000830

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.00712

Alfa

AF:

0.00125

Hom.:

Bravo

AF:

0.00682

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00900

AC:

1092

Asia WGS

AF:

0.0150

AC:

AN:

3478

EpiCase

AF:

0.0000548

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.084

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.63

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.74

MetaRNN

Benign

0.0022

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.0

MutationTaster

Benign

0.97

PrimateAI

Benign

0.44

PROVEAN

Benign

0.16

REVEL

Benign

0.044

Sift

Benign

0.48

Sift4G

Benign

0.89

Polyphen

0.19

Vest4

0.25

MutPred

0.23

Gain of ubiquitination at N1072 (P = 0.0198);

MPC

0.22

ClinPred

0.011

GERP RS

2.4

Varity_R

0.024

gMVP

0.12

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