Genetic Variant EHBP1:p.Gln227Leu (chr2-62858451-A-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015252.5(EHBP1):c.680A>T(p.Gln227Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,459,808 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/24 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: 0.0000027 ( 1 hom. )

Consequence

EHBP1
NM_015252.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.48

Publications

0 publications found

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:

ENSG00000226605 (HGNC:):

ENSG00000226605 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09507519).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015252.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EHBP1	NM_001142616.3	MANE Select	c.635-718A>T		intron	N/A	NP_001136088.1	Q8NDI1-3
EHBP1	NM_001354212.1		c.680A>T	p.Gln227Leu	missense	Exon 8 of 25	NP_001341141.1	Q8NDI1-1
EHBP1	NM_001354213.1		c.680A>T	p.Gln227Leu	missense	Exon 8 of 25	NP_001341142.1	Q8NDI1-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EHBP1	ENST00000263991.9	TSL:1	c.680A>T	p.Gln227Leu	missense	Exon 8 of 25	ENSP00000263991.5	Q8NDI1-1
EHBP1	ENST00000431489.6	TSL:1 MANE Select	c.635-718A>T		intron	N/A	ENSP00000403783.1	Q8NDI1-3
EHBP1	ENST00000405289.5	TSL:1	c.635-718A>T		intron	N/A	ENSP00000385524.1	Q8NDI1-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000799

AC:

AN:

250258

AF XY:

0.0000148

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1459808

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726128

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33456

American (AMR)

AF:

0.00

AC:

AN:

44552

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26108

East Asian (EAS)

AF:

0.00

AC:

AN:

39640

South Asian (SAS)

AF:

0.0000466

AC:

AN:

85826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53200

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110964

Other (OTH)

AF:

0.00

AC:

AN:

60298

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.30

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.020

Eigen

Benign

-0.047

Eigen_PC

Benign

0.11

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.63

M_CAP

Benign

0.033

MetaRNN

Benign

0.095

MetaSVM

Benign

-0.64

MutationAssessor

Benign

1.8

PhyloP100

4.5

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-1.3

REVEL

Benign

0.10

Sift

Benign

0.23

Sift4G

Benign

0.36

Polyphen

0.037

Vest4

0.39

MutPred

0.13

Loss of methylation at K232 (P = 0.0428)

MVP

0.34

MPC

0.11

ClinPred

0.37

GERP RS

5.0

Varity_R

0.13

gMVP

0.26

Mutation Taster

=86/14

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.20

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.20

Position offset: -45

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over