rs3737224

chr1-156909788-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001080471.3(PEAR1):c.1449C>T(p.Pro483=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 1,613,558 control chromosomes in the GnomAD database, including 12,908 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.13 (1429 hom., cov: 33)
  • Exomes 𝑓: 0.11 (11479 hom.)
• Consequence: PEAR1 NM_001080471.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.868

Genes affected

PEAR1 (HGNC:33631): (platelet endothelial aggregation receptor 1) PEAR1 is a platelet receptor that signals upon the formation of platelet-platelet contacts independent of platelet activation and secondary to platelet aggregation (Nanda et al., 2005 [PubMed 15851471]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP7: Synonymous conserved (PhyloP=-0.868 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.322 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PEAR1	NM_001080471.3	c.1449C>T	p.Pro483=	synonymous_variant	12/23	ENST00000292357.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PEAR1	ENST00000292357.8	c.1449C>T	p.Pro483=	synonymous_variant	12/23	5	NM_001080471.3	P1
PEAR1	ENST00000338302.7	c.1449C>T	p.Pro483=	synonymous_variant	13/24	5		P1
PEAR1	ENST00000469390.5	n.1177C>T		non_coding_transcript_exon_variant	7/18	2

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19840 AN: 152138 Hom.: 1423 Cov.: 33

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.131

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.335

Gnomad SAS AF: 0.186

Gnomad FIN AF: 0.120

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.130

GnomAD3 exomes AF: 0.135 AC: 33888 AN: 250876 Hom.: 2852 AF XY: 0.135 AC XY: 18326 AN XY: 135572

Gnomad AFR exome AF: 0.149

Gnomad AMR exome AF: 0.103

Gnomad ASJ exome AF: 0.0980

Gnomad EAS exome AF: 0.335

Gnomad SAS exome AF: 0.177

Gnomad FIN exome AF: 0.129

Gnomad NFE exome AF: 0.104

Gnomad OTH exome AF: 0.127

GnomAD4 exome AF: 0.115 AC: 167527 AN: 1461302 Hom.: 11479 Cov.: 34 AF XY: 0.117 AC XY: 84770 AN XY: 726866

Gnomad4 AFR exome AF: 0.149

Gnomad4 AMR exome AF: 0.107

Gnomad4 ASJ exome AF: 0.0955

Gnomad4 EAS exome AF: 0.355

Gnomad4 SAS exome AF: 0.175

Gnomad4 FIN exome AF: 0.126

Gnomad4 NFE exome AF: 0.100

Gnomad4 OTH exome AF: 0.124

GnomAD4 genome AF: 0.130 AC: 19855 AN: 152256 Hom.: 1429 Cov.: 33 AF XY: 0.134 AC XY: 9947 AN XY: 74456

Gnomad4 AFR AF: 0.146

Gnomad4 AMR AF: 0.123

Gnomad4 ASJ AF: 0.102

Gnomad4 EAS AF: 0.335

Gnomad4 SAS AF: 0.187

Gnomad4 FIN AF: 0.120

Gnomad4 NFE AF: 0.106

Gnomad4 OTH AF: 0.133

Alfa AF: 0.109 Hom.: 1218

Bravo AF: 0.131

Asia WGS AF: 0.246 AC: 853 AN: 3478

EpiCase AF: 0.105

EpiControl AF: 0.0990

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
Cadd	Benign	8.0
Dann	Benign	0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs3737224; hg19: chr1-156879580; COSMIC: COSV52771991; COSMIC: COSV52771991;