Variant 11-64854770-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006795.4(EHD1):c.1168A>G(p.Ile390Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000831 in 1,608,234 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00045 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00087 ( 1 hom. )

Consequence

EHD1
NM_006795.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.94

Variant links:

Genes affected

EHD1 (HGNC:3242): (EH domain containing 1) This gene belongs to a highly conserved gene family encoding EPS15 homology (EH) domain-containing proteins. The protein-binding EH domain was first noted in EPS15, a substrate for the epidermal growth factor receptor. The EH domain has been shown to be an important motif in proteins involved in protein-protein interactions and in intracellular sorting. The protein encoded by this gene is thought to play a role in the endocytosis of IGF1 receptors. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2013]

EHD1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13618371).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
EHD1	NM_006795.4 linkuse as main transcript	c.1168A>G	p.Ile390Val	missense_variant	5/5	ENST00000320631.8	NP_006786.2
EHD1	NM_001282445.2 linkuse as main transcript	c.1210A>G	p.Ile404Val	missense_variant	6/6		NP_001269374.1
EHD1	NM_001282444.2 linkuse as main transcript	c.1168A>G	p.Ile390Val	missense_variant	7/7		NP_001269373.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EHD1	ENST00000320631.8 linkuse as main transcript	c.1168A>G	p.Ile390Val	missense_variant	5/5	1	NM_006795.4	ENSP00000320516	P1

Frequencies

GnomAD3 genomes

AF:

0.000454

AC:

AN:

151956

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000839

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000402

AC:

AN:

246302

Hom.:

AF XY:

0.000389

AC XY:

AN XY:

133572

show subpopulations

Gnomad AFR exome

AF:

0.000248

Gnomad AMR exome

AF:

0.000203

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000760

Gnomad OTH exome

AF:

0.000328

GnomAD4 exome

AF:

0.000870

AC:

1267

AN:

1456278

Hom.:

Cov.:

AF XY:

0.000843

AC XY:

611

AN XY:

724646

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.000201

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000835

Gnomad4 NFE exome

AF:

0.00109

Gnomad4 OTH exome

AF:

0.000596

GnomAD4 genome

AF:

0.000454

AC:

AN:

151956

Hom.:

Cov.:

AF XY:

0.000377

AC XY:

AN XY:

74220

show subpopulations

Gnomad4 AFR

AF:

0.000145

Gnomad4 AMR

AF:

0.000393

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000839

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000961

Hom.:

Bravo

AF:

0.000476

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00116

AC:

ExAC

AF:

0.000338

AC:

EpiCase

AF:

0.000981

EpiControl

AF:

0.000474

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

Mar 02, 2023

The c.1168A>G (p.I390V) alteration is located in exon 5 (coding exon 5) of the EHD1 gene. This alteration results from a A to G substitution at nucleotide position 1168, causing the isoleucine (I) at amino acid position 390 to be replaced by a valine (V). 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

Benign

0.34

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.30

T;T;T;.

Eigen

Benign

0.16

Eigen_PC

Benign

0.20

FATHMM_MKL

Uncertain

0.78

LIST_S2

Uncertain

0.92

.;D;D;D

M_CAP

Benign

0.018

MetaRNN

Benign

0.14

T;T;T;T

MetaSVM

Benign

-0.82

MutationAssessor

Uncertain

2.7

M;.;M;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-0.81

N;.;N;N

REVEL

Benign

0.13

Sift

Benign

0.050

D;.;D;D

Sift4G

Benign

0.096

T;T;T;T

Polyphen

0.30

B;.;B;.

Vest4

0.44

MVP

0.52

MPC

0.73

ClinPred

0.11

GERP RS

3.4

Varity_R

0.089

gMVP

0.47

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