rs12041331

Variant names:

• chr1-156899922-G-A
• rs12041331
• NM_001080471.3:c.-9-3996G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 93 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PEAR1	NM_001080471.3	c.-9-3996G>A		intron_variant	Intron 1 of 22	ENST00000292357.8	NP_001073940.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PEAR1	ENST00000292357.8	c.-9-3996G>A		intron_variant	Intron 1 of 22	5	NM_001080471.3	ENSP00000292357.7
PEAR1	ENST00000338302.7	c.-107-2266G>A		intron_variant	Intron 1 of 23	5		ENSP00000344465.3
PEAR1	ENST00000455314.5	c.-9-3996G>A		intron_variant	Intron 1 of 5	2		ENSP00000389742.1
PEAR1	ENST00000444016.5	n.-9-3996G>A		intron_variant	Intron 1 of 6	3		ENSP00000397870.1

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

African (AFR) AF: 0.374 AC: 15507 AN: 41422

American (AMR) AF: 0.204 AC: 3109 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 417 AN: 3468

East Asian (EAS) AF: 0.430 AC: 2214 AN: 5154

South Asian (SAS) AF: 0.335 AC: 1614 AN: 4816

European-Finnish (FIN) AF: 0.0532 AC: 564 AN: 10600

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.0889 AC: 6043 AN: 67962

Other (OTH) AF: 0.192 AC: 406 AN: 2110

Alfa AF: 0.133 Hom.: 6512

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
PhyloP100		-3.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12041331; hg19: chr1-156869714;