rs57731889

Positions:

• chr1-156912469-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001080471.3(PEAR1):​c.2081-25C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 1,607,396 control chromosomes in the GnomAD database, including 15,286 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 0.12 (1805 hom., cov: 32)
  • Exomes 𝑓: 0.10 (13481 hom.)
• Consequence: PEAR1 NM_001080471.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0860

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]

PEAR1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.432 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PEAR1	NM_001080471.3	c.2081-25C>T		intron_variant		ENST00000292357.8	NP_001073940.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PEAR1	ENST00000292357.8	c.2081-25C>T		intron_variant		5	NM_001080471.3	ENSP00000292357.7
PEAR1	ENST00000338302.7	c.2081-25C>T		intron_variant		5		ENSP00000344465.3
PEAR1	ENST00000469390.5	n.1809-25C>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.125 AC: 18973 AN: 152108 Hom.: 1797 Cov.: 32

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.0724

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.0709

Gnomad EAS AF: 0.447

Gnomad SAS AF: 0.270

Gnomad FIN AF: 0.0565

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0719

Gnomad OTH AF: 0.125

GnomAD3 exomes AF: 0.166 AC: 40898 AN: 245812 Hom.: 5891 AF XY: 0.161 AC XY: 21457 AN XY: 132966

Gnomad AFR exome AF: 0.141

Gnomad AMR exome AF: 0.352

Gnomad ASJ exome AF: 0.0745

Gnomad EAS exome AF: 0.469

Gnomad SAS exome AF: 0.256

Gnomad FIN exome AF: 0.0536

Gnomad NFE exome AF: 0.0723

Gnomad OTH exome AF: 0.131

GnomAD4 exome AF: 0.101 AC: 147235 AN: 1455170 Hom.: 13481 Cov.: 32 AF XY: 0.105 AC XY: 75666 AN XY: 723400

Gnomad4 AFR exome AF: 0.140

Gnomad4 AMR exome AF: 0.336

Gnomad4 ASJ exome AF: 0.0728

Gnomad4 EAS exome AF: 0.449

Gnomad4 SAS exome AF: 0.250

Gnomad4 FIN exome AF: 0.0541

Gnomad4 NFE exome AF: 0.0690

Gnomad4 OTH exome AF: 0.116

GnomAD4 genome AF: 0.125 AC: 18998 AN: 152226 Hom.: 1805 Cov.: 32 AF XY: 0.130 AC XY: 9661 AN XY: 74424

Gnomad4 AFR AF: 0.138

Gnomad4 AMR AF: 0.232

Gnomad4 ASJ AF: 0.0709

Gnomad4 EAS AF: 0.447

Gnomad4 SAS AF: 0.270

Gnomad4 FIN AF: 0.0565

Gnomad4 NFE AF: 0.0718

Gnomad4 OTH AF: 0.129

Alfa AF: 0.0930 Hom.: 256

Bravo AF: 0.137

Asia WGS AF: 0.365 AC: 1268 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.7
DANN	Benign	0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs57731889; hg19: chr1-156882261; COSMIC: COSV52773263; COSMIC: COSV52773263;