rs4661012

Positions:

• chr1-156915699-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.*901T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 152,134 control chromosomes in the GnomAD database, including 10,455 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 0.36 (10455 hom., cov: 33)
  • Exomes 𝑓: 0.21 (0 hom.)
• Consequence: PEAR1 NM_001080471.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.448

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.532 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PEAR1	NM_001080471.3	c.*901T>G		3_prime_UTR_variant	23/23	ENST00000292357.8	NP_001073940.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PEAR1	ENST00000292357.8	c.*901T>G		3_prime_UTR_variant	23/23	5	NM_001080471.3	ENSP00000292357.7
PEAR1	ENST00000338302.7	c.*901T>G		3_prime_UTR_variant	24/24	5		ENSP00000344465.3
PEAR1	ENST00000469390.5	n.3743T>G		non_coding_transcript_exon_variant	18/18	2

Frequencies

GnomAD3 genomes AF: 0.364 AC: 55393 AN: 151992 Hom.: 10446 Cov.: 33

Gnomad AFR AF: 0.294

Gnomad AMI AF: 0.302

Gnomad AMR AF: 0.454

Gnomad ASJ AF: 0.382

Gnomad EAS AF: 0.548

Gnomad SAS AF: 0.539

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.360

Gnomad OTH AF: 0.370

GnomAD4 exome AF: 0.208 AC: 5 AN: 24 Hom.: 0 Cov.: 0 AF XY: 0.222 AC XY: 4 AN XY: 18

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.188

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.364 AC: 55423 AN: 152110 Hom.: 10455 Cov.: 33 AF XY: 0.369 AC XY: 27421 AN XY: 74340

Gnomad4 AFR AF: 0.294

Gnomad4 AMR AF: 0.455

Gnomad4 ASJ AF: 0.382

Gnomad4 EAS AF: 0.548

Gnomad4 SAS AF: 0.538

Gnomad4 FIN AF: 0.371

Gnomad4 NFE AF: 0.360

Gnomad4 OTH AF: 0.368

Alfa AF: 0.358 Hom.: 4082

Bravo AF: 0.366

Asia WGS AF: 0.516 AC: 1794 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.6
DANN	Benign	0.75

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: rs4661012; hg19: chr1-156885491;