Variant chr1-156913423-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001080471.3(PEAR1):c.2544C>A(p.Asn848Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 1,613,822 control chromosomes in the GnomAD database, including 14,677 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.16 ( 2082 hom., cov: 33)

Exomes 𝑓: 0.12 ( 12595 hom. )

Consequence

PEAR1
NM_001080471.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.632

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 Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0037869513).

BP6

Variant 1-156913423-C-A is Benign according to our data. Variant chr1-156913423-C-A is described in ClinVar as [Benign]. Clinvar id is 1243276.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PEAR1	NM_001080471.3 linkuse as main transcript	c.2544C>A	p.Asn848Lys	missense_variant	20/23	ENST00000292357.8	NP_001073940.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
PEAR1	ENST00000292357.8 linkuse as main transcript	c.2544C>A	p.Asn848Lys	missense_variant	20/23	5	NM_001080471.3	ENSP00000292357	P1
PEAR1	ENST00000338302.7 linkuse as main transcript	c.2544C>A	p.Asn848Lys	missense_variant	21/24	5		ENSP00000344465	P1
PEAR1	ENST00000469390.5 linkuse as main transcript	n.2272C>A		non_coding_transcript_exon_variant	15/18	2

Frequencies

GnomAD3 genomes

AF:

0.157

AC:

23856

AN:

152108

Hom.:

2077

Cov.:

show subpopulations

Gnomad AFR

AF:

0.224

Gnomad AMI

AF:

0.132

Gnomad AMR

AF:

0.130

Gnomad ASJ

AF:

0.109

Gnomad EAS

AF:

0.305

Gnomad SAS

AF:

0.168

Gnomad FIN

AF:

0.148

Gnomad MID

AF:

0.111

Gnomad NFE

AF:

0.115

Gnomad OTH

AF:

0.143

GnomAD3 exomes

AF:

0.142

AC:

35571

AN:

250654

Hom.:

3011

AF XY:

0.140

AC XY:

19023

AN XY:

135650

show subpopulations

Gnomad AFR exome

AF:

0.226

Gnomad AMR exome

AF:

0.103

Gnomad ASJ exome

AF:

0.104

Gnomad EAS exome

AF:

0.301

Gnomad SAS exome

AF:

0.163

Gnomad FIN exome

AF:

0.152

Gnomad NFE exome

AF:

0.112

Gnomad OTH exome

AF:

0.131

GnomAD4 exome

AF:

0.122

AC:

178088

AN:

1461596

Hom.:

12595

Cov.:

AF XY:

0.123

AC XY:

89381

AN XY:

727120

show subpopulations

Gnomad4 AFR exome

AF:

0.225

Gnomad4 AMR exome

AF:

0.108

Gnomad4 ASJ exome

AF:

0.104

Gnomad4 EAS exome

AF:

0.333

Gnomad4 SAS exome

AF:

0.160

Gnomad4 FIN exome

AF:

0.148

Gnomad4 NFE exome

AF:

0.108

Gnomad4 OTH exome

AF:

0.132

GnomAD4 genome

AF:

0.157

AC:

23873

AN:

152226

Hom.:

2082

Cov.:

AF XY:

0.160

AC XY:

11896

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.224

Gnomad4 AMR

AF:

0.130

Gnomad4 ASJ

AF:

0.109

Gnomad4 EAS

AF:

0.305

Gnomad4 SAS

AF:

0.168

Gnomad4 FIN

AF:

0.148

Gnomad4 NFE

AF:

0.115

Gnomad4 OTH

AF:

0.146

Alfa

AF:

0.126

Hom.:

718

Bravo

AF:

0.158

TwinsUK

AF:

0.104

AC:

387

ALSPAC

AF:

0.0947

AC:

365

ESP6500AA

AF:

0.227

AC:

1001

ESP6500EA

AF:

0.115

AC:

992

ExAC

AF:

0.144

AC:

17459

Asia WGS

AF:

0.234

AC:

813

AN:

3478

EpiCase

AF:

0.110

EpiControl

AF:

0.104

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 18, 2020	This variant is associated with the following publications: (PMID: 29407631) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.45

CADD

Benign

3.6

DANN

Benign

0.68

DEOGEN2

Benign

0.0078

T;T

Eigen

Benign

-0.85

Eigen_PC

Benign

-0.85

FATHMM_MKL

Benign

0.37

LIST_S2

Benign

0.27

.;T

MetaRNN

Benign

0.0038

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.4

L;L

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.92

N;N

REVEL

Benign

0.12

Sift

Benign

0.81

T;T

Sift4G

Benign

0.82

T;T

Polyphen

0.057

B;B

Vest4

0.047

MutPred

0.11

Gain of glycosylation at N848 (P = 0.0055);Gain of glycosylation at N848 (P = 0.0055);

MPC

0.18

ClinPred

0.0036

GERP RS

2.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.11

gMVP

0.25

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