17-64350416-T-C

Position:

• chr17-64350416-T-C

Variant summary

Our verdict is Benign. Variant got -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

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=0.0047064424).
• BP6: Variant 17-64350416-T-C is Benign according to our data. Variant chr17-64350416-T-C is described in ClinVar as [Benign]. Clinvar id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PECAM1	NM_000442.5	c.2008A>G	p.Arg670Gly	missense_variant	12/16	ENST00000563924.6	NP_000433.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PECAM1	ENST00000563924.6	c.2008A>G	p.Arg670Gly	missense_variant	12/16	1	NM_000442.5	ENSP00000457421.1

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

Gnomad4 AFR exome AF: 0.138

Gnomad4 AMR exome AF: 0.376

Gnomad4 ASJ exome AF: 0.413

Gnomad4 EAS exome AF: 0.483

Gnomad4 SAS exome AF: 0.391

Gnomad4 FIN exome AF: 0.521

Gnomad4 NFE exome AF: 0.488

Gnomad4 OTH exome AF: 0.436

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

Gnomad4 AFR AF: 0.141

Gnomad4 AMR AF: 0.388

Gnomad4 ASJ AF: 0.425

Gnomad4 EAS AF: 0.530

Gnomad4 SAS AF: 0.415

Gnomad4 FIN AF: 0.522

Gnomad4 NFE AF: 0.494

Gnomad4 OTH AF: 0.362

Alfa AF: 0.413 Hom.: 2325

Bravo AF: 0.357

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

Three Vessel Coronary Disease Benign:1

Benign, no assertion criteria provided

clinical testing

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

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Computational scores

Source: dbNSFP v4.3

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
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

Publications

LitVar

Other links and lift over

dbSNP: rs1131012; hg19: -;