Variant 2-62993546-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_001142616.3(EHBP1):c.2750T>C(p.Leu917Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,442,968 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

EHBP1
NM_001142616.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.95

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:

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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=0.073688865).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EHBP1	NM_001142616.3 linkuse as main transcript	c.2750T>C	p.Leu917Pro	missense_variant	17/23	ENST00000431489.6	NP_001136088.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EHBP1	ENST00000431489.6 linkuse as main transcript	c.2750T>C	p.Leu917Pro	missense_variant	17/23	1	NM_001142616.3	ENSP00000403783	A1	Q8NDI1-3
EHBP1-AS1	ENST00000650490.1 linkuse as main transcript	n.572+20013A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000139

AC:

AN:

1442968

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

717958

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000240

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

Jun 29, 2023

The c.2963T>C (p.L988P) alteration is located in exon 19 (coding exon 18) of the EHBP1 gene. This alteration results from a T to C substitution at nucleotide position 2963, causing the leucine (L) at amino acid position 988 to be replaced by a proline (P). 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

0.072

BayesDel_addAF

Benign

-0.0086

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.0061

.;.;T;.

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.015

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.72

.;T;T;T

M_CAP

Benign

0.010

MetaRNN

Benign

0.074

T;T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.0

.;.;N;.

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.73

N;N;N;N

REVEL

Benign

0.16

Sift

Benign

0.18

T;T;T;T

Sift4G

Benign

0.21

T;T;T;T

Polyphen

0.0030

B;B;B;B

Vest4

0.29

MutPred

0.23

.;.;Loss of stability (P = 0.0148);.;

MVP

0.27

MPC

0.17

ClinPred

0.23

GERP RS

3.4

Varity_R

0.15

gMVP

0.53

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