rs11264580

Positions:

• chr1-156908739-T-C
• chr1-156908739-T-G

Variant summary

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

The NM_001080471.3(PEAR1):​c.1200T>C​(p.His400His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 1,567,880 control chromosomes in the GnomAD database, including 18,492 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 0.18 (2615 hom., cov: 33)
  • Exomes 𝑓: 0.14 (15877 hom.)
• Consequence: PEAR1 NM_001080471.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.480

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=-0.6).
• 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	Protein	UniProt
PEAR1	NM_001080471.3	c.1200T>C	p.His400His	synonymous_variant	10/23	ENST00000292357.8	NP_001073940.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PEAR1	ENST00000292357.8	c.1200T>C	p.His400His	synonymous_variant	10/23	5	NM_001080471.3	ENSP00000292357.7
PEAR1	ENST00000338302.7	c.1200T>C	p.His400His	synonymous_variant	11/24	5		ENSP00000344465.3
PEAR1	ENST00000469390.5	n.928T>C		non_coding_transcript_exon_variant	5/18	2

Frequencies

GnomAD3 genomes AF: 0.178 AC: 26981 AN: 151960 Hom.: 2608 Cov.: 33

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.335

Gnomad SAS AF: 0.229

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.162

GnomAD3 exomes AF: 0.169 AC: 30645 AN: 181572 Hom.: 2895 AF XY: 0.168 AC XY: 16504 AN XY: 98468

Gnomad AFR exome AF: 0.241

Gnomad AMR exome AF: 0.177

Gnomad ASJ exome AF: 0.118

Gnomad EAS exome AF: 0.327

Gnomad SAS exome AF: 0.217

Gnomad FIN exome AF: 0.138

Gnomad NFE exome AF: 0.124

Gnomad OTH exome AF: 0.156

GnomAD4 exome AF: 0.141 AC: 199560 AN: 1415796 Hom.: 15877 Cov.: 34 AF XY: 0.143 AC XY: 100318 AN XY: 701494

Gnomad4 AFR exome AF: 0.247

Gnomad4 AMR exome AF: 0.180

Gnomad4 ASJ exome AF: 0.117

Gnomad4 EAS exome AF: 0.355

Gnomad4 SAS exome AF: 0.216

Gnomad4 FIN exome AF: 0.143

Gnomad4 NFE exome AF: 0.123

Gnomad4 OTH exome AF: 0.151

GnomAD4 genome AF: 0.178 AC: 27012 AN: 152084 Hom.: 2615 Cov.: 33 AF XY: 0.182 AC XY: 13519 AN XY: 74350

Gnomad4 AFR AF: 0.244

Gnomad4 AMR AF: 0.182

Gnomad4 ASJ AF: 0.122

Gnomad4 EAS AF: 0.335

Gnomad4 SAS AF: 0.230

Gnomad4 FIN AF: 0.153

Gnomad4 NFE AF: 0.128

Gnomad4 OTH AF: 0.165

Alfa AF: 0.134 Hom.: 596

Bravo AF: 0.181

Asia WGS AF: 0.272 AC: 942 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	7.7
DANN	Benign	0.55

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: rs11264580; hg19: chr1-156878531; COSMIC: COSV52770643; COSMIC: COSV52770643;