rs281865545

Positions:

• chr17-64377836-C-G
• chr17-64377836-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_000442.5(PECAM1):​c.373G>C​(p.Val125Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.479 in 474,850 control chromosomes in the GnomAD database, including 55,152 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 0.46 (16619 hom., cov: 30)
  • Exomes 𝑓: 0.49 (38533 hom.)
• Consequence: PECAM1 NM_000442.5 missense
• Clinical Significance: Benign no assertion criteria provided B:2 O:1
• Conservation: PhyloP100: -0.159

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0066434443).
• BP6: Variant 17-64377836-C-G is Benign according to our data. Variant chr17-64377836-C-G is described in ClinVar as [Benign]. Clinvar id is 156304.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.557 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PECAM1	NM_000442.5	c.373G>C	p.Val125Leu	missense_variant	3/16	ENST00000563924.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PECAM1	ENST00000563924.6	c.373G>C	p.Val125Leu	missense_variant	3/16	1	NM_000442.5	P1

Frequencies

GnomAD3 genomes AF: 0.465 AC: 70500 AN: 151672 Hom.: 16601 Cov.: 30

Gnomad AFR AF: 0.388

Gnomad AMI AF: 0.640

Gnomad AMR AF: 0.532

Gnomad ASJ AF: 0.541

Gnomad EAS AF: 0.436

Gnomad SAS AF: 0.576

Gnomad FIN AF: 0.467

Gnomad MID AF: 0.583

Gnomad NFE AF: 0.482

Gnomad OTH AF: 0.510

GnomAD4 exome AF: 0.485 AC: 156723 AN: 323062 Hom.: 38533 Cov.: 0 AF XY: 0.487 AC XY: 82009 AN XY: 168560

Gnomad4 AFR exome AF: 0.387

Gnomad4 AMR exome AF: 0.564

Gnomad4 ASJ exome AF: 0.556

Gnomad4 EAS exome AF: 0.460

Gnomad4 SAS exome AF: 0.583

Gnomad4 FIN exome AF: 0.469

Gnomad4 NFE exome AF: 0.480

Gnomad4 OTH exome AF: 0.483

GnomAD4 genome AF: 0.465 AC: 70564 AN: 151788 Hom.: 16619 Cov.: 30 AF XY: 0.469 AC XY: 34815 AN XY: 74154

Gnomad4 AFR AF: 0.388

Gnomad4 AMR AF: 0.533

Gnomad4 ASJ AF: 0.541

Gnomad4 EAS AF: 0.436

Gnomad4 SAS AF: 0.575

Gnomad4 FIN AF: 0.467

Gnomad4 NFE AF: 0.482

Gnomad4 OTH AF: 0.514

Alfa AF: 0.189 Hom.: 245

Bravo AF: 0.469

ClinVar

Significance: Benign

Submissions summary: Benign:2 Other:1

Revision: no assertion criteria provided

Submissions by phenotype

PLATELET-ENDOTHELIAL CELL ADHESION MOLECULE 1 POLYMORPHISM Benign:1

Benign, no assertion criteria provided

literature only

OMIM

Feb 01, 1996

- -

Three Vessel Coronary Disease Benign:1

Benign, no assertion criteria provided

clinical testing

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

-

- -

not provided Other:1

not provided, no classification provided

literature only

ClinVar Staff, National Center for Biotechnology Information (NCBI)

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
CADD	Benign	6.7
LIST_S2	Benign	0.71	T;T;T;T
MetaRNN	Benign	0.0066	T;T;T;T
PROVEAN	Benign	0.0	N;N;N;N
Sift	Benign	0.21	T;T;T;T
Sift4G	Benign	0.12	T;.;.;.
Vest4		0.17
gMVP		0.29

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs281865545; hg19: -;