Genetic Variant EHBP1:p.Leu917Val (chr2-62993545-C-G) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6BS2_Supporting

The NM_001142616.3(EHBP1):c.2749C>G(p.Leu917Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0012 in 1,594,258 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00082 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 1 hom. )

Consequence

EHBP1
NM_001142616.3 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.34

Variant links:

Genes affected

EHBP1 (HGNC:29144): (EH domain binding protein 1) This gene encodes an Eps15 homology domain binding protein. The encoded protein may play a role in endocytic trafficking. A single nucleotide polymorphism in this gene is associated with an aggressive form of prostate cancer. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Feb 2010]

EHBP1 links:

EHBP1-AS1 (HGNC:55766): (EHBP1 antisense RNA 1)

EHBP1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011664897).

BP6

Variant 2-62993545-C-G is Benign according to our data. Variant chr2-62993545-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 3053880.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 125 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EHBP1	NM_001142616.3 link	c.2749C>G	p.Leu917Val	missense_variant	Exon 17 of 23	ENST00000431489.6	NP_001136088.1	Q8NDI1-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EHBP1	ENST00000431489.6 link	c.2749C>G	p.Leu917Val	missense_variant	Exon 17 of 23	1	NM_001142616.3	ENSP00000403783.1		Q8NDI1-3

Frequencies

GnomAD3 genomes

AF:

0.000823

AC:

125

AN:

151914

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000394

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.000190

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00143

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00101

AC:

250

AN:

247598

Hom.:

AF XY:

0.00108

AC XY:

145

AN XY:

133972

show subpopulations

Gnomad AFR exome

AF:

0.000311

Gnomad AMR exome

AF:

0.000509

Gnomad ASJ exome

AF:

0.000200

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00142

Gnomad FIN exome

AF:

0.000232

Gnomad NFE exome

AF:

0.00155

Gnomad OTH exome

AF:

0.000669

GnomAD4 exome

AF:

0.00124

AC:

1788

AN:

1442228

Hom.:

Cov.:

AF XY:

0.00125

AC XY:

899

AN XY:

717576

show subpopulations

Gnomad4 AFR exome

AF:

0.000211

Gnomad4 AMR exome

AF:

0.000498

Gnomad4 ASJ exome

AF:

0.000314

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00195

Gnomad4 FIN exome

AF:

0.000285

Gnomad4 NFE exome

AF:

0.00138

Gnomad4 OTH exome

AF:

0.000826

GnomAD4 genome

AF:

0.000822

AC:

125

AN:

152030

Hom.:

Cov.:

AF XY:

0.000781

AC XY:

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.000241

Gnomad4 AMR

AF:

0.000393

Gnomad4 ASJ

AF:

0.000577

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.000190

Gnomad4 NFE

AF:

0.00143

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00118

Hom.:

Bravo

AF:

0.000725

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00151

AC:

ExAC

AF:

0.000980

AC:

119

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

EHBP1-related disorder

Benign:1

Dec 14, 2020

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.010

.;.;T;.

Eigen

Uncertain

0.26

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.91

.;D;D;D

M_CAP

Benign

0.012

MetaRNN

Benign

0.012

T;T;T;T

MetaSVM

Benign

-0.79

MutationAssessor

Benign

0.69

.;.;N;.

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.54

N;N;N;N

REVEL

Benign

0.14

Sift

Benign

0.46

T;T;T;T

Sift4G

Benign

0.51

T;T;T;T

Polyphen

0.33

B;B;B;B

Vest4

0.14

MVP

0.43

MPC

0.10

ClinPred

0.028

GERP RS

5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.10

gMVP

0.23

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