Genetic Variant PECAM1:p.Ser563Asn (chr17-64356203-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_000442.5(PECAM1):c.1688G>A(p.Ser563Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.443 in 474,152 control chromosomes in the GnomAD database, including 50,015 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/7 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.38 ( 12830 hom., cov: 28)

Exomes 𝑓: 0.47 ( 37185 hom. )

Consequence

PECAM1
NM_000442.5 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.10

Publications

46 publications found

Variant links:

Genes affected

PECAM1 (HGNC:8823): (platelet and endothelial cell adhesion molecule 1) The protein encoded by this gene is found on the surface of platelets, monocytes, neutrophils, and some types of T-cells, and makes up a large portion of endothelial cell intercellular junctions. The encoded protein is a member of the immunoglobulin superfamily and is likely involved in leukocyte migration, angiogenesis, and integrin activation. [provided by RefSeq, May 2010]

PECAM1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003622979).

BP6

Variant 17-64356203-C-T is Benign according to our data. Variant chr17-64356203-C-T is described in ClinVar as Benign. ClinVar VariationId is 812624.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.513 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PECAM1	NM_000442.5 link	c.1688G>A	p.Ser563Asn	missense_variant	Exon 8 of 16	ENST00000563924.6	NP_000433.4	P16284-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PECAM1	ENST00000563924.6 link	c.1688G>A	p.Ser563Asn	missense_variant	Exon 8 of 16	1	NM_000442.5	ENSP00000457421.1		P16284-1

Frequencies

GnomAD3 genomes

AF:

0.382

AC:

57631

AN:

150962

Hom.:

12837

Cov.:

show subpopulations

Gnomad AFR

AF:

0.140

Gnomad AMI

AF:

0.323

Gnomad AMR

AF:

0.386

Gnomad ASJ

AF:

0.426

Gnomad EAS

AF:

0.529

Gnomad SAS

AF:

0.414

Gnomad FIN

AF:

0.523

Gnomad MID

AF:

0.293

Gnomad NFE

AF:

0.492

Gnomad OTH

AF:

0.367

GnomAD4 exome

AF:

0.472

AC:

152449

AN:

323070

Hom.:

37185

Cov.:

AF XY:

0.474

AC XY:

79820

AN XY:

168558

show subpopulations

African (AFR)

AF:

0.138

AC:

1254

AN:

9068

American (AMR)

AF:

0.383

AC:

6300

AN:

16454

Ashkenazi Jewish (ASJ)

AF:

0.413

AC:

4214

AN:

10194

East Asian (EAS)

AF:

0.488

AC:

13095

AN:

26858

South Asian (SAS)

AF:

0.413

AC:

4157

AN:

10054

European-Finnish (FIN)

AF:

0.522

AC:

20486

AN:

39224

Middle Eastern (MID)

AF:

0.324

AC:

443

AN:

1366

European-Non Finnish (NFE)

AF:

0.493

AC:

94125

AN:

191024

Other (OTH)

AF:

0.445

AC:

8375

AN:

18828

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

4835

9670

14504

19339

24174

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

582

1164

1746

2328

2910

<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:

0.381

AC:

57625

AN:

151082

Hom.:

12830

Cov.:

AF XY:

0.383

AC XY:

28217

AN XY:

73724

show subpopulations

African (AFR)

AF:

0.140

AC:

5776

AN:

41244

American (AMR)

AF:

0.386

AC:

5813

AN:

15068

Ashkenazi Jewish (ASJ)

AF:

0.426

AC:

1478

AN:

3468

East Asian (EAS)

AF:

0.529

AC:

2665

AN:

5034

South Asian (SAS)

AF:

0.414

AC:

1985

AN:

4792

European-Finnish (FIN)

AF:

0.523

AC:

5407

AN:

10346

Middle Eastern (MID)

AF:

0.298

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.492

AC:

33356

AN:

67828

Other (OTH)

AF:

0.364

AC:

766

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1595

3190

4784

6379

7974

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

558

1116

1674

2232

2790

<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:

0.401

Hom.:

1760

Bravo

AF:

0.356

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Three Vessel Coronary Disease

Benign:1

Department of Cardiology, Chinese Academy of Medical Sciences, Fuwai Hospital

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

CADD

Benign

(source)

DEOGEN2

Benign

0.031

LIST_S2

Benign

0.52

MetaRNN

Benign

0.0036

PhyloP100

2.1

PROVEAN

Benign

-1.6

Sift

Benign

0.058

Sift4G

Uncertain

0.046

Vest4

0.23

gMVP

0.34

Splicing

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over