dbSNP rs3737224: PEAR1:p.Pro483Pro (chr1-156909788-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001080471.3(PEAR1):c.1449C>T(p.Pro483Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 1,613,558 control chromosomes in the GnomAD database, including 12,908 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 0.13 ( 1429 hom., cov: 33)

Exomes 𝑓: 0.11 ( 11479 hom. )

Consequence

PEAR1
NM_001080471.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.868

Publications

27 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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP7

Synonymous conserved (PhyloP=-0.868 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.322 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PEAR1	NM_001080471.3 link	c.1449C>T	p.Pro483Pro	synonymous_variant	Exon 12 of 23	ENST00000292357.8	NP_001073940.1	Q5VY43

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PEAR1	ENST00000292357.8 link	c.1449C>T	p.Pro483Pro	synonymous_variant	Exon 12 of 23	5	NM_001080471.3	ENSP00000292357.7	Q5VY43
PEAR1	ENST00000338302.7 link	c.1449C>T	p.Pro483Pro	synonymous_variant	Exon 13 of 24	5		ENSP00000344465.3	Q5VY43
PEAR1	ENST00000469390.5 link	n.1177C>T		non_coding_transcript_exon_variant	Exon 7 of 18	2
PEAR1	ENST00000482505.1 link	n.-169C>T		upstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.130

AC:

19840

AN:

152138

Hom.:

1423

Cov.:

show subpopulations

Gnomad AFR

AF:

0.146

Gnomad AMI

AF:

0.131

Gnomad AMR

AF:

0.123

Gnomad ASJ

AF:

0.102

Gnomad EAS

AF:

0.335

Gnomad SAS

AF:

0.186

Gnomad FIN

AF:

0.120

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.106

Gnomad OTH

AF:

0.130

GnomAD2 exomes

AF:

0.135

AC:

33888

AN:

250876

AF XY:

0.135

show subpopulations

Gnomad AFR exome

AF:

0.149

Gnomad AMR exome

AF:

0.103

Gnomad ASJ exome

AF:

0.0980

Gnomad EAS exome

AF:

0.335

Gnomad FIN exome

AF:

0.129

Gnomad NFE exome

AF:

0.104

Gnomad OTH exome

AF:

0.127

GnomAD4 exome

AF:

0.115

AC:

167527

AN:

1461302

Hom.:

11479

Cov.:

AF XY:

0.117

AC XY:

84770

AN XY:

726866

show subpopulations

African (AFR)

AF:

0.149

AC:

4985

AN:

33474

American (AMR)

AF:

0.107

AC:

4797

AN:

44680

Ashkenazi Jewish (ASJ)

AF:

0.0955

AC:

2494

AN:

26114

East Asian (EAS)

AF:

0.355

AC:

14070

AN:

39686

South Asian (SAS)

AF:

0.175

AC:

15074

AN:

86204

European-Finnish (FIN)

AF:

0.126

AC:

6725

AN:

53378

Middle Eastern (MID)

AF:

0.108

AC:

624

AN:

5764

European-Non Finnish (NFE)

AF:

0.100

AC:

111302

AN:

1111652

Other (OTH)

AF:

0.124

AC:

7456

AN:

60350

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

8754

17508

26261

35015

43769

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4248

8496

12744

16992

21240

<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:

0.130

AC:

19855

AN:

152256

Hom.:

1429

Cov.:

AF XY:

0.134

AC XY:

9947

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.146

AC:

6051

AN:

41544

American (AMR)

AF:

0.123

AC:

1877

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.102

AC:

354

AN:

3472

East Asian (EAS)

AF:

0.335

AC:

1727

AN:

5156

South Asian (SAS)

AF:

0.187

AC:

901

AN:

4828

European-Finnish (FIN)

AF:

0.120

AC:

1270

AN:

10616

Middle Eastern (MID)

AF:

0.109

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.106

AC:

7242

AN:

68026

Other (OTH)

AF:

0.133

AC:

282

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

891

1781

2672

3562

4453

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

232

464

696

928

1160

<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:

0.114

Hom.:

3142

Bravo

AF:

0.131

Asia WGS

AF:

0.246

AC:

853

AN:

3478

EpiCase

AF:

0.105

EpiControl

AF:

0.0990

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

8.0

(source)

DANN

Benign

0.52

PhyloP100

-0.87

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over