Genetic Variant EHBP1:p.Thr1097Ala (chr2-63045077-A-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001142616.3(EHBP1):c.3289A>G(p.Thr1097Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

EHBP1
NM_001142616.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.72

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:

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

EHBP1-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.3289A>G	p.Thr1097Ala	missense	Exon 22 of 23	NP_001136088.1	Q8NDI1-3
EHBP1	NM_001354212.1		c.3502A>G	p.Thr1168Ala	missense	Exon 24 of 25	NP_001341141.1	Q8NDI1-1
EHBP1	NM_001354213.1		c.3502A>G	p.Thr1168Ala	missense	Exon 24 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.3289A>G	p.Thr1097Ala	missense	Exon 22 of 23	ENSP00000403783.1	Q8NDI1-3
EHBP1	ENST00000263991.9	TSL:1	c.3502A>G	p.Thr1168Ala	missense	Exon 24 of 25	ENSP00000263991.5	Q8NDI1-1
EHBP1	ENST00000405289.5	TSL:1	c.3397A>G	p.Thr1133Ala	missense	Exon 22 of 23	ENSP00000385524.1	Q8NDI1-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1410670

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

696258

African (AFR)

AF:

0.00

AC:

AN:

32212

American (AMR)

AF:

0.00

AC:

AN:

37776

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25328

East Asian (EAS)

AF:

0.00

AC:

AN:

36850

South Asian (SAS)

AF:

0.00

AC:

AN:

80164

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49936

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5692

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1084342

Other (OTH)

AF:

0.00

AC:

AN:

58370

GnomAD4 genome

Cov.:

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

Pathogenic

0.77

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Uncertain

-0.050

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.33

Eigen

Pathogenic

0.87

Eigen_PC

Pathogenic

0.83

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.021

MetaRNN

Uncertain

0.47

MetaSVM

Uncertain

-0.066

MutationAssessor

Pathogenic

2.9

PhyloP100

5.7

PrimateAI

Pathogenic

0.83

PROVEAN

Uncertain

-4.0

REVEL

Uncertain

0.48

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0060

Polyphen

0.99

Vest4

0.56

MutPred

0.28

Loss of phosphorylation at T1168 (P = 0.0483)

MVP

0.63

MPC

1.6

ClinPred

0.99

GERP RS

5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.9

Varity_R

0.92

gMVP

0.74

Mutation Taster

=35/65

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over