1-156899255-G-T

Variant names:

• chr1-156899255-G-T
• rs12566888
• NM_001080471.3:c.-9-4663G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001080471.3(PEAR1):​c.-9-4663G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 151,962 control chromosomes in the GnomAD database, including 8,443 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 0.26 (8443 hom., cov: 32)
• Consequence: PEAR1 NM_001080471.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.442
• Publications: 56 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.563 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080471.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PEAR1	NM_001080471.3	MANE Select	c.-9-4663G>T		intron	N/A	NP_001073940.1
	PEAR1	NM_001353682.2		c.-347-4663G>T		intron	N/A	NP_001340611.1
	PEAR1	NM_001353683.2		c.-506-2933G>T		intron	N/A	NP_001340612.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PEAR1	ENST00000292357.8	TSL:5 MANE Select	c.-9-4663G>T		intron	N/A	ENSP00000292357.7
	PEAR1	ENST00000971373.1		c.-178-2933G>T		intron	N/A	ENSP00000641432.1
	PEAR1	ENST00000338302.7	TSL:5	c.-107-2933G>T		intron	N/A	ENSP00000344465.3

Frequencies

GnomAD3 genomes AF: 0.256 AC: 38906 AN: 151844 Hom.: 8415 Cov.: 32

Gnomad AFR AF: 0.569

Gnomad AMI AF: 0.0899

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.457

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.0536

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.0932

Gnomad OTH AF: 0.235

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

GnomAD4 genome AF: 0.257 AC: 38987 AN: 151962 Hom.: 8443 Cov.: 32 AF XY: 0.256 AC XY: 19004 AN XY: 74264

African (AFR) AF: 0.569 AC: 23522 AN: 41332

American (AMR) AF: 0.225 AC: 3439 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 412 AN: 3472

East Asian (EAS) AF: 0.458 AC: 2359 AN: 5156

South Asian (SAS) AF: 0.355 AC: 1698 AN: 4788

European-Finnish (FIN) AF: 0.0536 AC: 569 AN: 10612

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.0932 AC: 6339 AN: 68000

Other (OTH) AF: 0.237 AC: 502 AN: 2114

Alfa AF: 0.154 Hom.: 11464

Bravo AF: 0.280

Asia WGS AF: 0.410 AC: 1426 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.3
DANN	Benign	0.50
PhyloP100		0.44
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: rs12566888; hg19: chr1-156869047;