rs12041331

chr1-156899922-G-A

Variant summary

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

The NM_001080471.3(PEAR1):c.-9-3996G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 152,004 control chromosomes in the GnomAD database, including 4,394 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 0.20 (4394 hom., cov: 32)
• Consequence: PEAR1 NM_001080471.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.41

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 (EAS) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PEAR1	NM_001080471.3	c.-9-3996G>A		intron_variant		ENST00000292357.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PEAR1	ENST00000292357.8	c.-9-3996G>A		intron_variant		5	NM_001080471.3	P1
PEAR1	ENST00000338302.7	c.-107-2266G>A		intron_variant		5		P1
PEAR1	ENST00000455314.5	c.-9-3996G>A		intron_variant		2
PEAR1	ENST00000444016.5	c.-9-3996G>A		intron_variant, NMD_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.197 AC: 29964 AN: 151886 Hom.: 4380 Cov.: 32

Gnomad AFR AF: 0.374

Gnomad AMI AF: 0.0899

Gnomad AMR AF: 0.203

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.429

Gnomad SAS AF: 0.336

Gnomad FIN AF: 0.0532

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.0889

Gnomad OTH AF: 0.190

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

GnomAD4 genome AF: 0.197 AC: 30010 AN: 152004 Hom.: 4394 Cov.: 32 AF XY: 0.198 AC XY: 14684 AN XY: 74292

Gnomad4 AFR AF: 0.374

Gnomad4 AMR AF: 0.204

Gnomad4 ASJ AF: 0.120

Gnomad4 EAS AF: 0.430

Gnomad4 SAS AF: 0.335

Gnomad4 FIN AF: 0.0532

Gnomad4 NFE AF: 0.0889

Gnomad4 OTH AF: 0.192

Alfa AF: 0.122 Hom.: 2219

Bravo AF: 0.212

Asia WGS AF: 0.380 AC: 1324 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	0.028
Dann	Benign	0.62

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: rs12041331; hg19: chr1-156869714;