1-156913423-C-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

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

Publications

28 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PEAR1	NM_001080471.3	MANE Select	c.2544C>A	p.Asn848Lys	missense	Exon 20 of 23	NP_001073940.1
PEAR1	NM_001353682.2		c.2352C>A	p.Asn784Lys	missense	Exon 20 of 23	NP_001340611.1
PEAR1	NM_001353683.2		c.2352C>A	p.Asn784Lys	missense	Exon 21 of 24	NP_001340612.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PEAR1	ENST00000292357.8	TSL:5 MANE Select	c.2544C>A	p.Asn848Lys	missense	Exon 20 of 23	ENSP00000292357.7
PEAR1	ENST00000338302.7	TSL:5	c.2544C>A	p.Asn848Lys	missense	Exon 21 of 24	ENSP00000344465.3
PEAR1	ENST00000469390.5	TSL:2	n.2272C>A		non_coding_transcript_exon	Exon 15 of 18

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

GnomAD2 exomes

AF:

0.142

AC:

35571

AN:

250654

AF XY:

0.140

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 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

African (AFR)

AF:

0.225

AC:

7535

AN:

33474

American (AMR)

AF:

0.108

AC:

4823

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.104

AC:

2727

AN:

26134

East Asian (EAS)

AF:

0.333

AC:

13238

AN:

39700

South Asian (SAS)

AF:

0.160

AC:

13798

AN:

86256

European-Finnish (FIN)

AF:

0.148

AC:

7865

AN:

53152

Middle Eastern (MID)

AF:

0.104

AC:

601

AN:

5768

European-Non Finnish (NFE)

AF:

0.108

AC:

119545

AN:

1111998

Other (OTH)

AF:

0.132

AC:

7956

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

10350

20701

31051

41402

51752

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4498

8996

13494

17992

22490

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.157

AC:

23873

AN:

152226

Hom.:

2082

Cov.:

AF XY:

0.160

AC XY:

11896

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.224

AC:

9293

AN:

41534

American (AMR)

AF:

0.130

AC:

1986

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.109

AC:

378

AN:

3468

East Asian (EAS)

AF:

0.305

AC:

1573

AN:

5152

South Asian (SAS)

AF:

0.168

AC:

812

AN:

4828

European-Finnish (FIN)

AF:

0.148

AC:

1570

AN:

10612

Middle Eastern (MID)

AF:

0.119

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.115

AC:

7797

AN:

68012

Other (OTH)

AF:

0.146

AC:

309

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1018

2036

3054

4072

5090

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

266

532

798

1064

1330

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

Feb 18, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 29407631)

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.45

CADD

Benign

3.6

(source)

DANN

Benign

0.68

DEOGEN2

Benign

0.0078

Eigen

Benign

-0.85

Eigen_PC

Benign

-0.85

FATHMM_MKL

Benign

0.37

LIST_S2

Benign

0.27

MetaRNN

Benign

0.0038

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.4

PhyloP100

0.63

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.92

REVEL

Benign

0.12

Sift

Benign

0.81

Sift4G

Benign

0.82

Polyphen

0.057

Vest4

0.047

MutPred

0.11

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

Mutation Taster

=78/22

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over