Variant 11-64854546-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_006795.4(EHD1):c.1392C>T(p.Gly464=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00293 in 1,614,128 control chromosomes in the GnomAD database, including 99 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 47 hom., cov: 33)

Exomes 𝑓: 0.0017 ( 52 hom. )

Consequence

EHD1
NM_006795.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.43

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 Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 11-64854546-G-A is Benign according to our data. Variant chr11-64854546-G-A is described in ClinVar as [Benign]. Clinvar id is 783617.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.43 with no splicing effect.

BA1

GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.053 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
EHD1	NM_006795.4 linkuse as main transcript	c.1392C>T	p.Gly464=	synonymous_variant	5/5	ENST00000320631.8	NP_006786.2
EHD1	NM_001282445.2 linkuse as main transcript	c.1434C>T	p.Gly478=	synonymous_variant	6/6		NP_001269374.1
EHD1	NM_001282444.2 linkuse as main transcript	c.1392C>T	p.Gly464=	synonymous_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.1392C>T	p.Gly464=	synonymous_variant	5/5	1	NM_006795.4	ENSP00000320516	P1

Frequencies

GnomAD3 genomes

AF:

0.0146

AC:

2219

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0498

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00674

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000368

Gnomad OTH

AF:

0.0101

GnomAD3 exomes

AF:

0.00401

AC:

1009

AN:

251464

Hom.:

AF XY:

0.00303

AC XY:

412

AN XY:

135922

show subpopulations

Gnomad AFR exome

AF:

0.0520

Gnomad AMR exome

AF:

0.00312

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.000462

Gnomad NFE exome

AF:

0.000281

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.00172

AC:

2512

AN:

1461852

Hom.:

Cov.:

AF XY:

0.00146

AC XY:

1060

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.0551

Gnomad4 AMR exome

AF:

0.00320

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000104

Gnomad4 FIN exome

AF:

0.000337

Gnomad4 NFE exome

AF:

0.000255

Gnomad4 OTH exome

AF:

0.00338

GnomAD4 genome

AF:

0.0146

AC:

2218

AN:

152276

Hom.:

Cov.:

AF XY:

0.0147

AC XY:

1097

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.0497

Gnomad4 AMR

AF:

0.00673

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.000368

Gnomad4 OTH

AF:

0.00995

Alfa

AF:

0.00566

Hom.:

Bravo

AF:

0.0164

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

6.0

DANN

Benign

0.79

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