Genetic Variant EHBP1:p.Pro957Thr (chr2-62993665-C-A) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BS2_Supporting

The NM_001142616.3(EHBP1):c.2869C>A(p.Pro957Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000637 in 1,570,536 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000063 ( 0 hom. )

Consequence

EHBP1
NM_001142616.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.80

Publications

1 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:

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

EHBP1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BS2

High AC in GnomAdExome4 at 9 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142616.3. 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.2869C>A	p.Pro957Thr	missense	Exon 17 of 23	NP_001136088.1	Q8NDI1-3
EHBP1	NM_001354212.1		c.3082C>A	p.Pro1028Thr	missense	Exon 19 of 25	NP_001341141.1	Q8NDI1-1
EHBP1	NM_001354213.1		c.3082C>A	p.Pro1028Thr	missense	Exon 19 of 25	NP_001341142.1	Q8NDI1-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EHBP1	ENST00000431489.6	TSL:1 MANE Select	c.2869C>A	p.Pro957Thr	missense	Exon 17 of 23	ENSP00000403783.1	Q8NDI1-3
EHBP1	ENST00000263991.9	TSL:1	c.3082C>A	p.Pro1028Thr	missense	Exon 19 of 25	ENSP00000263991.5	Q8NDI1-1
EHBP1	ENST00000405289.5	TSL:1	c.2977C>A	p.Pro993Thr	missense	Exon 17 of 23	ENSP00000385524.1	Q8NDI1-2

Frequencies

GnomAD3 genomes

AF:

0.00000672

AC:

AN:

148816

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:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000149

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000164

AC:

AN:

243340

AF XY:

0.0000151

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000310

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000272

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000633

AC:

AN:

1421720

Hom.:

Cov.:

AF XY:

0.00000425

AC XY:

AN XY:

706608

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32520

American (AMR)

AF:

0.0000239

AC:

AN:

41876

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24834

East Asian (EAS)

AF:

0.00

AC:

AN:

39204

South Asian (SAS)

AF:

0.00

AC:

AN:

78350

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51564

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5598

European-Non Finnish (NFE)

AF:

0.00000734

AC:

AN:

1089384

Other (OTH)

AF:

0.00

AC:

AN:

58390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000672

AC:

AN:

148816

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

72610

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40098

American (AMR)

AF:

0.00

AC:

AN:

14938

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3462

East Asian (EAS)

AF:

0.00

AC:

AN:

5148

South Asian (SAS)

AF:

0.00

AC:

AN:

4734

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9942

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000149

AC:

AN:

67238

Other (OTH)

AF:

0.00

AC:

AN:

2040

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000247

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

0.18

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Uncertain

0.060

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.64

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.98

M_CAP

Benign

0.025

MetaRNN

Uncertain

0.48

MetaSVM

Benign

-0.52

MutationAssessor

Benign

2.0

PhyloP100

7.8

PrimateAI

Uncertain

0.70

PROVEAN

Uncertain

-4.1

REVEL

Uncertain

0.44

Sift

Uncertain

0.0020

Sift4G

Benign

0.093

Polyphen

1.0

Vest4

0.60

MutPred

0.26

Loss of glycosylation at P1028 (P = 0.0284)

MVP

0.44

MPC

0.55

ClinPred

0.87

GERP RS

5.9

Varity_R

0.64

gMVP

0.39

Mutation Taster

=53/47

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over