Variant 1-156909841-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001080471.3(PEAR1):c.1502T>C(p.Val501Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000205 in 1,613,782 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00022 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00020 ( 0 hom. )

Consequence

PEAR1
NM_001080471.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.96

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.003858894).

BP6

Variant 1-156909841-T-C is Benign according to our data. Variant chr1-156909841-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2455137.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PEAR1	NM_001080471.3 linkuse as main transcript	c.1502T>C	p.Val501Ala	missense_variant	12/23	ENST00000292357.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
PEAR1	ENST00000292357.8 linkuse as main transcript	c.1502T>C	p.Val501Ala	missense_variant	12/23	5	NM_001080471.3	P1
PEAR1	ENST00000338302.7 linkuse as main transcript	c.1502T>C	p.Val501Ala	missense_variant	13/24	5		P1
PEAR1	ENST00000469390.5 linkuse as main transcript	n.1230T>C		non_coding_transcript_exon_variant	7/18	2

Frequencies

GnomAD3 genomes

AF:

0.000223

AC:

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00893

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000430

AC:

108

AN:

251136

Hom.:

AF XY:

0.000413

AC XY:

AN XY:

135754

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00865

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000132

Gnomad OTH exome

AF:

0.000979

GnomAD4 exome

AF:

0.000203

AC:

297

AN:

1461596

Hom.:

Cov.:

AF XY:

0.000195

AC XY:

142

AN XY:

727078

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00785

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000450

Gnomad4 OTH exome

AF:

0.000662

GnomAD4 genome

AF:

0.000223

AC:

AN:

152186

Hom.:

Cov.:

AF XY:

0.000229

AC XY:

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00893

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000643

Hom.:

Bravo

AF:

0.000212

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000296

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 14, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.050

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.72

Cadd

Benign

Dann

Benign

0.63

DEOGEN2

Benign

0.0050

T;T

Eigen

Benign

-0.85

Eigen_PC

Benign

-0.64

FATHMM_MKL

Benign

0.15

M_CAP

Benign

0.0021

MetaRNN

Benign

0.0039

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-0.56

N;N

MutationTaster

Benign

0.93

N;N

PrimateAI

Benign

0.36

PROVEAN

Benign

2.1

N;N

REVEL

Benign

0.062

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;B

Vest4

0.042

MVP

0.26

MPC

0.19

ClinPred

0.013

GERP RS

3.0

Varity_R

0.017

gMVP

0.36

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over