Variant 2-62987954-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 0P and 3B. BP4_ModerateBS2_Supporting

The NM_015252.5(EHBP1):c.2737G>T(p.Asp913Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.0000245 in 1,594,654 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000026 ( 1 hom. )

Consequence

EHBP1
NM_015252.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.69

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 -3 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.1475757).

BS2

High AC in GnomAdExome4 at 38 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/exons	MANE	Protein	UniProt
EHBP1	NM_001142616.3 link	c.2609-2762G>T		intron_variant		ENST00000431489.6	NP_001136088.1	Q8NDI1-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EHBP1	ENST00000431489.6 link	c.2609-2762G>T		intron_variant		1	NM_001142616.3	ENSP00000403783.1		Q8NDI1-3

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151970

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000242

AC:

AN:

247482

Hom.:

AF XY:

0.0000374

AC XY:

AN XY:

133844

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000299

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000335

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000890

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.0000263

AC:

AN:

1442684

Hom.:

Cov.:

AF XY:

0.0000334

AC XY:

AN XY:

718202

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000347

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000108

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000127

Gnomad4 OTH exome

AF:

0.0000670

GnomAD4 genome

AF:

0.00000658

AC:

AN:

151970

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74202

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000189

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000165

AC:

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

Nov 08, 2024

The c.2737G>T (p.D913Y) alteration is located in exon 17 (coding exon 16) of the EHBP1 gene. This alteration results from a G to T substitution at nucleotide position 2737, causing the aspartic acid (D) at amino acid position 913 to be replaced by a tyrosine (Y). 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

0.14

BayesDel_addAF

Benign

-0.016

BayesDel_noAF

Benign

-0.16

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.026

T;.

Eigen

Uncertain

0.19

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.89

D;D

M_CAP

Benign

0.044

MetaRNN

Benign

0.15

T;T

MetaSVM

Benign

-0.69

MutationAssessor

Benign

1.8

L;.

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-2.0

N;N

REVEL

Uncertain

0.35

Sift

Uncertain

0.014

D;D

Sift4G

Uncertain

0.058

T;T

Polyphen

0.30

B;B

Vest4

0.50

MVP

0.46

MPC

0.25

ClinPred

0.41

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.16

gMVP

0.39

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