rs281865545

Variant names:

• chr17-64377836-C-G
• rs281865545
• NM_000442.5:c.373G>C

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 72 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000442.5. 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
	PECAM1	NM_000442.5	MANE Select	c.373G>C	p.Val125Leu	missense	Exon 3 of 16	NP_000433.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PECAM1	ENST00000563924.6	TSL:1 MANE Select	c.373G>C	p.Val125Leu	missense	Exon 3 of 16	ENSP00000457421.1	P16284-1
	PECAM1	ENST00000904885.1		c.373G>C	p.Val125Leu	missense	Exon 3 of 17	ENSP00000574944.1
	PECAM1	ENST00000904891.1		c.373G>C	p.Val125Leu	missense	Exon 3 of 17	ENSP00000574950.1

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

African (AFR) AF: 0.387 AC: 3513 AN: 9066

American (AMR) AF: 0.564 AC: 9283 AN: 16456

Ashkenazi Jewish (ASJ) AF: 0.556 AC: 5671 AN: 10194

East Asian (EAS) AF: 0.460 AC: 12353 AN: 26862

South Asian (SAS) AF: 0.583 AC: 5858 AN: 10052

European-Finnish (FIN) AF: 0.469 AC: 18353 AN: 39172

Middle Eastern (MID) AF: 0.597 AC: 816 AN: 1366

European-Non Finnish (NFE) AF: 0.480 AC: 91775 AN: 191062

Other (OTH) AF: 0.483 AC: 9101 AN: 18832

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

African (AFR) AF: 0.388 AC: 16042 AN: 41350

American (AMR) AF: 0.533 AC: 8119 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.541 AC: 1878 AN: 3470

East Asian (EAS) AF: 0.436 AC: 2242 AN: 5140

South Asian (SAS) AF: 0.575 AC: 2763 AN: 4802

European-Finnish (FIN) AF: 0.467 AC: 4919 AN: 10540

Middle Eastern (MID) AF: 0.572 AC: 167 AN: 292

European-Non Finnish (NFE) AF: 0.482 AC: 32768 AN: 67938

Other (OTH) AF: 0.514 AC: 1086 AN: 2112

Alfa AF: 0.189 Hom.: 245

Bravo AF: 0.469

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	PECAM1 POLYMORPHISM (1)
-	-	1	Three Vessel Coronary Disease (1)
-	-	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
CADD	Benign	6.7
LIST_S2	Benign	0.71	T
MetaRNN	Benign	0.0066	T
PhyloP100		-0.16
PROVEAN	Benign	0.0	N
Sift	Benign	0.21	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

Other links and lift over

dbSNP: rs281865545;