dbSNP rs191293806: EHBP1:p.Ala149Thr (chr2-62826219-G-A) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBS2_Supporting

The NM_001142616.3(EHBP1):c.445G>A(p.Ala149Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000153 in 1,605,148 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00016 ( 1 hom. )

Consequence

EHBP1
NM_001142616.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.99

Publications

2 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007275939).

BP6

Variant 2-62826219-G-A is Benign according to our data. Variant chr2-62826219-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2406608.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 14 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.445G>A	p.Ala149Thr	missense	Exon 6 of 23	NP_001136088.1	Q8NDI1-3
EHBP1	NM_001354212.1		c.445G>A	p.Ala149Thr	missense	Exon 6 of 25	NP_001341141.1	Q8NDI1-1
EHBP1	NM_001354213.1		c.445G>A	p.Ala149Thr	missense	Exon 6 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.445G>A	p.Ala149Thr	missense	Exon 6 of 23	ENSP00000403783.1	Q8NDI1-3
EHBP1	ENST00000263991.9	TSL:1	c.445G>A	p.Ala149Thr	missense	Exon 6 of 25	ENSP00000263991.5	Q8NDI1-1
EHBP1	ENST00000405289.5	TSL:1	c.445G>A	p.Ala149Thr	missense	Exon 5 of 23	ENSP00000385524.1	Q8NDI1-2

Frequencies

GnomAD3 genomes

AF:

0.0000921

AC:

AN:

152018

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:

0.00250

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000107

AC:

AN:

242074

AF XY:

0.0000995

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000311

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00118

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000180

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000160

AC:

232

AN:

1453012

Hom.:

Cov.:

AF XY:

0.000149

AC XY:

108

AN XY:

722468

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32912

American (AMR)

AF:

0.0000235

AC:

AN:

42498

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25788

East Asian (EAS)

AF:

0.00507

AC:

200

AN:

39470

South Asian (SAS)

AF:

0.0000239

AC:

AN:

83782

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53332

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5732

European-Non Finnish (NFE)

AF:

0.0000207

AC:

AN:

1109430

Other (OTH)

AF:

0.0000999

AC:

AN:

60068

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

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:

0.0000920

AC:

AN:

152136

Hom.:

Cov.:

AF XY:

0.0000941

AC XY:

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41528

American (AMR)

AF:

0.00

AC:

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00251

AC:

AN:

5180

South Asian (SAS)

AF:

0.000207

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10580

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67984

Other (OTH)

AF:

0.00

AC:

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.0000818

Hom.:

Bravo

AF:

0.0000604

ExAC

AF:

0.0000906

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

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

0.043

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.56

CADD

Benign

(source)

DANN

Benign

0.84

DEOGEN2

Benign

0.0073

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.72

M_CAP

Benign

0.0035

MetaRNN

Benign

0.0073

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-2.2

PhyloP100

5.0

PrimateAI

Uncertain

0.77

PROVEAN

Benign

2.4

REVEL

Benign

0.10

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.23

MVP

0.043

MPC

0.097

ClinPred

0.023

GERP RS

4.3

Varity_R

0.060

gMVP

0.097

Mutation Taster

=85/15

polymorphism

(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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over