Genetic Variant PEBP1:p.His145Tyr (chr12-118144672-C-T) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_002567.4(PEBP1):c.433C>T(p.His145Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00807 in 1,614,092 control chromosomes in the GnomAD database, including 68 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0063 ( 4 hom., cov: 31)

Exomes 𝑓: 0.0083 ( 64 hom. )

Consequence

PEBP1
NM_002567.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0440

Publications

11 publications found

Variant links:

Genes affected

PEBP1 (HGNC:8630): (phosphatidylethanolamine binding protein 1) This gene encodes a member of the phosphatidylethanolamine-binding family of proteins and has been shown to modulate multiple signaling pathways, including the MAP kinase (MAPK), NF-kappa B, and glycogen synthase kinase-3 (GSK-3) signaling pathways. The encoded protein can be further processed to form a smaller cleavage product, hippocampal cholinergic neurostimulating peptide (HCNP), which may be involved in neural development. This gene has been implicated in numerous human cancers and may act as a metastasis suppressor gene. Multiple pseudogenes of this gene have been identified in the genome. [provided by RefSeq, Jul 2015]

PEBP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010391235).

BP6

Variant 12-118144672-C-T is Benign according to our data. Variant chr12-118144672-C-T is described in ClinVar as Benign. ClinVar VariationId is 775314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002567.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PEBP1	NM_002567.4	MANE Select	c.433C>T	p.His145Tyr	missense	Exon 4 of 4	NP_002558.1	P30086

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PEBP1	ENST00000261313.3	TSL:1 MANE Select	c.433C>T	p.His145Tyr	missense	Exon 4 of 4	ENSP00000261313.2	P30086
PEBP1	ENST00000874099.1		c.532C>T	p.His178Tyr	missense	Exon 4 of 4	ENSP00000544158.1
PEBP1	ENST00000874101.1		c.475C>T	p.His159Tyr	missense	Exon 4 of 4	ENSP00000544160.1

Frequencies

GnomAD3 genomes

AF:

0.00630

AC:

959

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00130

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00517

Gnomad ASJ

AF:

0.00490

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00707

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0105

Gnomad OTH

AF:

0.00623

GnomAD2 exomes

AF:

0.00643

AC:

1617

AN:

251392

AF XY:

0.00639

show subpopulations

Gnomad AFR exome

AF:

0.00166

Gnomad AMR exome

AF:

0.00376

Gnomad ASJ exome

AF:

0.00447

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00494

Gnomad NFE exome

AF:

0.0110

Gnomad OTH exome

AF:

0.00831

GnomAD4 exome

AF:

0.00825

AC:

12063

AN:

1461858

Hom.:

Cov.:

AF XY:

0.00818

AC XY:

5947

AN XY:

727232

show subpopulations

African (AFR)

AF:

0.00152

AC:

AN:

33480

American (AMR)

AF:

0.00389

AC:

174

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00375

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000209

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00635

AC:

339

AN:

53418

Middle Eastern (MID)

AF:

0.00521

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.00981

AC:

10904

AN:

1111998

Other (OTH)

AF:

0.00743

AC:

449

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

740

1479

2219

2958

3698

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

390

780

1170

1560

1950

<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:

0.00629

AC:

958

AN:

152234

Hom.:

Cov.:

AF XY:

0.00622

AC XY:

463

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.00130

AC:

AN:

41540

American (AMR)

AF:

0.00517

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00490

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00707

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0105

AC:

711

AN:

68014

Other (OTH)

AF:

0.00616

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

106

158

211

264

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.00864

Hom.:

Bravo

AF:

0.00596

TwinsUK

AF:

0.00863

AC:

ALSPAC

AF:

0.00649

AC:

ESP6500AA

AF:

0.00227

AC:

ESP6500EA

AF:

0.0119

AC:

102

ExAC

AF:

0.00716

AC:

869

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.00905

EpiControl

AF:

0.0100

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.58

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Uncertain

0.48

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.64

FATHMM_MKL

Benign

0.63

LIST_S2

Uncertain

0.93

MetaRNN

Benign

0.010

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.4

PhyloP100

-0.044

PrimateAI

Benign

0.35

PROVEAN

Uncertain

-3.3

REVEL

Benign

0.074

Sift

Benign

0.063

Sift4G

Uncertain

0.020

Polyphen

0.098

Vest4

0.15

MVP

0.47

MPC

0.44

ClinPred

0.071

GERP RS

-3.9

Varity_R

0.34

gMVP

0.60

Mutation Taster

=96/4

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

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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