Variant 11-64854734-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_006795.4(EHD1):c.1204T>A(p.Ser402Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

EHD1
NM_006795.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.19

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0635961).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
EHD1	NM_006795.4 linkuse as main transcript	c.1204T>A	p.Ser402Thr	missense_variant	5/5	ENST00000320631.8	NP_006786.2
EHD1	NM_001282445.2 linkuse as main transcript	c.1246T>A	p.Ser416Thr	missense_variant	6/6		NP_001269374.1
EHD1	NM_001282444.2 linkuse as main transcript	c.1204T>A	p.Ser402Thr	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.1204T>A	p.Ser402Thr	missense_variant	5/5	1	NM_006795.4	ENSP00000320516	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459876

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726396

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

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:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Dec 11, 2023

The c.1204T>A (p.S402T) alteration is located in exon 5 (coding exon 5) of the EHD1 gene. This alteration results from a T to A substitution at nucleotide position 1204, causing the serine (S) at amino acid position 402 to be replaced by a threonine (T). 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

0.062

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Benign

0.87

DEOGEN2

Benign

0.14

T;T;T;.

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.46

FATHMM_MKL

Benign

0.61

LIST_S2

Benign

0.53

.;T;T;T

M_CAP

Benign

0.0042

MetaRNN

Benign

0.064

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.33

N;.;N;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.49

PROVEAN

Benign

0.12

N;.;N;N

REVEL

Benign

0.017

Sift

Benign

0.60

T;.;T;T

Sift4G

Benign

0.62

T;T;T;T

Polyphen

0.0

B;.;B;.

Vest4

0.072

MutPred

0.32

Loss of loop (P = 0.0112);.;Loss of loop (P = 0.0112);.;

MVP

0.38

MPC

0.75

ClinPred

0.092

GERP RS

2.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.043

gMVP

0.33

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over