rs1131012

Variant names:

• chr17-64350416-T-C
• rs1131012
• NM_000442.5:c.2008A>G

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.2008A>G​(p.Arg670Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.439 in 429,034 control chromosomes in the GnomAD database, including 44,658 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 (13014 hom., cov: 31)
  • Exomes 𝑓: 0.47 (31644 hom.)
• Consequence: PECAM1 NM_000442.5 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 2.16
• Publications: 49 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=0.0047064424).
• BP6: Variant 17-64350416-T-C is Benign according to our data. Variant chr17-64350416-T-C is described in ClinVar as Benign. ClinVar VariationId is 812625.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.

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.2008A>G	p.Arg670Gly	missense	Exon 12 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.2008A>G	p.Arg670Gly	missense	Exon 12 of 16	ENSP00000457421.1	P16284-1
	PECAM1	ENST00000904885.1		c.2008A>G	p.Arg670Gly	missense	Exon 12 of 17	ENSP00000574944.1
	PECAM1	ENST00000904891.1		c.2008A>G	p.Arg670Gly	missense	Exon 12 of 17	ENSP00000574950.1

Frequencies

GnomAD3 genomes AF: 0.383 AC: 58172 AN: 151894 Hom.: 13021 Cov.: 31

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.324

Gnomad AMR AF: 0.388

Gnomad ASJ AF: 0.425

Gnomad EAS AF: 0.530

Gnomad SAS AF: 0.415

Gnomad FIN AF: 0.522

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.494

Gnomad OTH AF: 0.365

GnomAD4 exome AF: 0.470 AC: 130170 AN: 277022 Hom.: 31644 Cov.: 0 AF XY: 0.471 AC XY: 66612 AN XY: 141322

African (AFR) AF: 0.138 AC: 1105 AN: 8000

American (AMR) AF: 0.376 AC: 3756 AN: 9990

Ashkenazi Jewish (ASJ) AF: 0.413 AC: 3893 AN: 9426

East Asian (EAS) AF: 0.483 AC: 11927 AN: 24684

South Asian (SAS) AF: 0.391 AC: 1777 AN: 4546

European-Finnish (FIN) AF: 0.521 AC: 18909 AN: 36268

Middle Eastern (MID) AF: 0.319 AC: 416 AN: 1306

European-Non Finnish (NFE) AF: 0.488 AC: 80948 AN: 165748

Other (OTH) AF: 0.436 AC: 7439 AN: 17054

GnomAD4 genome AF: 0.383 AC: 58170 AN: 152012 Hom.: 13014 Cov.: 31 AF XY: 0.384 AC XY: 28541 AN XY: 74262

African (AFR) AF: 0.141 AC: 5865 AN: 41530

American (AMR) AF: 0.388 AC: 5915 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.425 AC: 1474 AN: 3468

East Asian (EAS) AF: 0.530 AC: 2742 AN: 5174

South Asian (SAS) AF: 0.415 AC: 2002 AN: 4820

European-Finnish (FIN) AF: 0.522 AC: 5493 AN: 10524

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.494 AC: 33533 AN: 67940

Other (OTH) AF: 0.362 AC: 764 AN: 2110

Alfa AF: 0.432 Hom.: 3201

Bravo AF: 0.357

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	Three Vessel Coronary Disease (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.044
CADD	Benign	19
DEOGEN2	Benign	0.0039	T
LIST_S2	Benign	0.31	T
MetaRNN	Benign	0.0047	T
PhyloP100		2.2
PROVEAN	Benign	2.8	N
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Vest4		0.18
gMVP		0.20

Splicing

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

Other links and lift over

dbSNP: rs1131012;