Variant 2-62826214-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001142616.3(EHBP1):c.440C>G(p.Ser147Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000206 in 1,456,688 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

EHBP1
NM_001142616.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.79

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:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EHBP1	NM_001142616.3 linkuse as main transcript	c.440C>G	p.Ser147Cys	missense_variant	6/23	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.440C>G	p.Ser147Cys	missense_variant	6/23	1	NM_001142616.3	ENSP00000403783	A1	Q8NDI1-3
	ENST00000452397.1 linkuse as main transcript	n.101G>C		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000407

AC:

AN:

245956

Hom.:

AF XY:

0.00000753

AC XY:

AN XY:

132876

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000554

Gnomad SAS 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:

0.00000206

AC:

AN:

1456688

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

724486

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000506

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

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

Aug 05, 2023

The c.440C>G (p.S147C) alteration is located in exon 6 (coding exon 5) of the EHBP1 gene. This alteration results from a C to G substitution at nucleotide position 440, causing the serine (S) at amino acid position 147 to be replaced by a cysteine (C). 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

0.13

BayesDel_addAF

Benign

-0.069

BayesDel_noAF

Benign

-0.17

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.14

.;T;T;T;.;T;.

Eigen

Pathogenic

0.75

Eigen_PC

Pathogenic

0.74

FATHMM_MKL

Uncertain

0.85

LIST_S2

Pathogenic

0.98

.;D;D;D;D;D;D

M_CAP

Benign

0.035

MetaRNN

Uncertain

0.49

T;T;T;T;T;T;T

MetaSVM

Benign

-0.51

MutationAssessor

Benign

1.8

L;.;.;.;L;L;L

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.78

PROVEAN

Uncertain

-3.5

D;D;D;D;D;D;D

REVEL

Uncertain

0.34

Sift

Uncertain

0.0040

D;D;D;D;D;D;D

Sift4G

Uncertain

0.0080

D;D;D;D;D;D;D

Polyphen

1.0

D;.;.;.;D;D;D

Vest4

0.58

MutPred

0.34

Loss of disorder (P = 0.0264);.;.;Loss of disorder (P = 0.0264);Loss of disorder (P = 0.0264);Loss of disorder (P = 0.0264);Loss of disorder (P = 0.0264);

MVP

0.27

MPC

0.49

ClinPred

0.97

GERP RS

5.4

Varity_R

0.54

gMVP

0.35

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.23

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.23

Position offset: -5

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