rs2644592

Positions:

• chr1-156905972-G-A
• chr1-156905972-G-C

Variant summary

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

The NM_001080471.3(PEAR1):​c.308-304G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.768 in 152,022 control chromosomes in the GnomAD database, including 45,431 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 0.77 (45431 hom., cov: 31)
• Consequence: PEAR1 NM_001080471.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.594

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.838 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PEAR1	NM_001080471.3	c.308-304G>A		intron_variant		ENST00000292357.8	NP_001073940.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PEAR1	ENST00000292357.8	c.308-304G>A		intron_variant		5	NM_001080471.3	ENSP00000292357	P1
PEAR1	ENST00000338302.7	c.308-304G>A		intron_variant		5		ENSP00000344465	P1
PEAR1	ENST00000455314.5	c.308-304G>A		intron_variant		2		ENSP00000389742
PEAR1	ENST00000444016.5	c.*129-304G>A		intron_variant, NMD_transcript_variant		3		ENSP00000397870

Frequencies

GnomAD3 genomes AF: 0.768 AC: 116681 AN: 151904 Hom.: 45410 Cov.: 31

Gnomad AFR AF: 0.655

Gnomad AMI AF: 0.860

Gnomad AMR AF: 0.758

Gnomad ASJ AF: 0.796

Gnomad EAS AF: 0.605

Gnomad SAS AF: 0.675

Gnomad FIN AF: 0.841

Gnomad MID AF: 0.791

Gnomad NFE AF: 0.844

Gnomad OTH AF: 0.785

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.768 AC: 116744 AN: 152022 Hom.: 45431 Cov.: 31 AF XY: 0.764 AC XY: 56771 AN XY: 74316

Gnomad4 AFR AF: 0.654

Gnomad4 AMR AF: 0.758

Gnomad4 ASJ AF: 0.796

Gnomad4 EAS AF: 0.604

Gnomad4 SAS AF: 0.675

Gnomad4 FIN AF: 0.841

Gnomad4 NFE AF: 0.844

Gnomad4 OTH AF: 0.783

Alfa AF: 0.829 Hom.: 85582

Bravo AF: 0.761

Asia WGS AF: 0.652 AC: 2270 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.3
DANN	Benign	0.55

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: rs2644592; hg19: chr1-156875764;