rs41273215

Positions:

• chr1-156912167-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.1952-80C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 1,520,274 control chromosomes in the GnomAD database, including 11,922 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 (1401 hom., cov: 32)
  • Exomes 𝑓: 0.11 (10521 hom.)
• Consequence: PEAR1 NM_001080471.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0610

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PEAR1	NM_001080471.3	c.1952-80C>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.1952-80C>T		intron_variant		5	NM_001080471.3	ENSP00000292357	P1
PEAR1	ENST00000338302.7	c.1952-80C>T		intron_variant		5		ENSP00000344465	P1
PEAR1	ENST00000469390.5	n.1680-80C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19760 AN: 152004 Hom.: 1395 Cov.: 32

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.131

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.332

Gnomad SAS AF: 0.174

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.129

GnomAD4 exome AF: 0.114 AC: 155321 AN: 1368152 Hom.: 10521 AF XY: 0.115 AC XY: 77443 AN XY: 672932

Gnomad4 AFR exome AF: 0.145

Gnomad4 AMR exome AF: 0.106

Gnomad4 ASJ exome AF: 0.0996

Gnomad4 EAS exome AF: 0.353

Gnomad4 SAS exome AF: 0.162

Gnomad4 FIN exome AF: 0.139

Gnomad4 NFE exome AF: 0.0995

Gnomad4 OTH exome AF: 0.124

GnomAD4 genome AF: 0.130 AC: 19775 AN: 152122 Hom.: 1401 Cov.: 32 AF XY: 0.134 AC XY: 9959 AN XY: 74360

Gnomad4 AFR AF: 0.142

Gnomad4 AMR AF: 0.123

Gnomad4 ASJ AF: 0.105

Gnomad4 EAS AF: 0.332

Gnomad4 SAS AF: 0.175

Gnomad4 FIN AF: 0.139

Gnomad4 NFE AF: 0.106

Gnomad4 OTH AF: 0.132

Alfa AF: 0.116 Hom.: 146

Bravo AF: 0.130

Asia WGS AF: 0.245 AC: 850 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	8.0
DANN	Benign	0.51

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: rs41273215; hg19: chr1-156881959; COSMIC: COSV52773585; COSMIC: COSV52773585;