Variant chr2-62771376-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BS2_Supporting

The NM_001142616.3(EHBP1):c.296C>T(p.Thr99Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000201 in 1,592,854 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000097 ( 0 hom. )

Consequence

EHBP1
NM_001142616.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.69

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 (HGNC:):

EHBP1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

BS2

High AC in GnomAd4 at 18 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 linkuse as main transcript	c.296C>T	p.Thr99Ile	missense_variant	5/23	ENST00000431489.6	NP_001136088.1	Q8NDI1-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EHBP1	ENST00000431489.6 linkuse as main transcript	c.296C>T	p.Thr99Ile	missense_variant	5/23	1	NM_001142616.3	ENSP00000403783.1		Q8NDI1-3

Frequencies

GnomAD3 genomes

AF:

0.000118

AC:

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000972

AC:

AN:

1440732

Hom.:

Cov.:

AF XY:

0.0000112

AC XY:

AN XY:

716374

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000190

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000182

Gnomad4 OTH exome

AF:

0.0000673

GnomAD4 genome

AF:

0.000118

AC:

AN:

152122

Hom.:

Cov.:

AF XY:

0.0000942

AC XY:

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000554

Hom.:

Bravo

AF:

0.000310

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 21, 2023

The c.296C>T (p.T99I) alteration is located in exon 5 (coding exon 4) of the EHBP1 gene. This alteration results from a C to T substitution at nucleotide position 296, causing the threonine (T) at amino acid position 99 to be replaced by an isoleucine (I). 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

0.33

BayesDel_addAF

Pathogenic

0.20

BayesDel_noAF

Pathogenic

0.15

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

.;.;T;.;T;.

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.90

.;D;D;D;D;D

M_CAP

Benign

0.026

MetaRNN

Uncertain

0.54

D;D;D;D;D;D

MetaSVM

Benign

-0.37

MutationAssessor

Uncertain

2.9

M;.;.;M;M;M

PrimateAI

Pathogenic

0.82

PROVEAN

Uncertain

-4.4

D;D;D;D;D;D

REVEL

Uncertain

0.37

Sift

Uncertain

0.029

D;D;D;D;D;D

Sift4G

Uncertain

0.0050

D;D;D;D;D;D

Polyphen

1.0

D;.;.;D;B;B

Vest4

0.78

MutPred

0.41

Loss of disorder (P = 0.0658);.;Loss of disorder (P = 0.0658);Loss of disorder (P = 0.0658);Loss of disorder (P = 0.0658);Loss of disorder (P = 0.0658);

MVP

0.53

MPC

0.20

ClinPred

0.98

GERP RS

5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.59

gMVP

0.52

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