dbSNP rs41299597: PEAR1:p.Ser802Cys (chr1-156912965-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_001080471.3(PEAR1):c.2405C>G(p.Ser802Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0197 in 1,614,078 control chromosomes in the GnomAD database, including 399 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.015 ( 31 hom., cov: 32)

Exomes 𝑓: 0.020 ( 368 hom. )

Consequence

PEAR1
NM_001080471.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.14

Publications

11 publications found

Variant links:

COSMIC-nc: COSV107346227

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0068558753).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0148 (2250/152278) while in subpopulation NFE AF = 0.0247 (1683/68010). AF 95% confidence interval is 0.0238. There are 31 homozygotes in GnomAd4. There are 1051 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 31 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PEAR1	NM_001080471.3 link	c.2405C>G	p.Ser802Cys	missense_variant	Exon 18 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.2405C>G	p.Ser802Cys	missense_variant	Exon 18 of 23	5	NM_001080471.3	ENSP00000292357.7	Q5VY43
PEAR1	ENST00000338302.7 link	c.2405C>G	p.Ser802Cys	missense_variant	Exon 19 of 24	5		ENSP00000344465.3	Q5VY43
PEAR1	ENST00000469390.5 link	n.2133C>G		non_coding_transcript_exon_variant	Exon 13 of 18	2

Frequencies

GnomAD3 genomes

AF:

0.0148

AC:

2250

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00372

Gnomad AMI

AF:

0.0198

Gnomad AMR

AF:

0.00530

Gnomad ASJ

AF:

0.0141

Gnomad EAS

AF:

0.00115

Gnomad SAS

AF:

0.0162

Gnomad FIN

AF:

0.0147

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.0247

Gnomad OTH

AF:

0.0110

GnomAD2 exomes

AF:

0.0155

AC:

3888

AN:

251172

AF XY:

0.0164

show subpopulations

Gnomad AFR exome

AF:

0.00388

Gnomad AMR exome

AF:

0.00431

Gnomad ASJ exome

AF:

0.0135

Gnomad EAS exome

AF:

0.00120

Gnomad FIN exome

AF:

0.0162

Gnomad NFE exome

AF:

0.0225

Gnomad OTH exome

AF:

0.0163

GnomAD4 exome

AF:

0.0203

AC:

29627

AN:

1461800

Hom.:

368

Cov.:

AF XY:

0.0205

AC XY:

14892

AN XY:

727208

show subpopulations

African (AFR)

AF:

0.00338

AC:

113

AN:

33478

American (AMR)

AF:

0.00458

AC:

205

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.0126

AC:

330

AN:

26136

East Asian (EAS)

AF:

0.000353

AC:

AN:

39700

South Asian (SAS)

AF:

0.0189

AC:

1633

AN:

86252

European-Finnish (FIN)

AF:

0.0164

AC:

876

AN:

53370

Middle Eastern (MID)

AF:

0.00748

AC:

AN:

5748

European-Non Finnish (NFE)

AF:

0.0228

AC:

25318

AN:

1112002

Other (OTH)

AF:

0.0181

AC:

1095

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

1731

3462

5193

6924

8655

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

854

1708

2562

3416

4270

<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:

0.0148

AC:

2250

AN:

152278

Hom.:

Cov.:

AF XY:

0.0141

AC XY:

1051

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.00370

AC:

154

AN:

41566

American (AMR)

AF:

0.00530

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0141

AC:

AN:

3468

East Asian (EAS)

AF:

0.00116

AC:

AN:

5184

South Asian (SAS)

AF:

0.0162

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.0147

AC:

156

AN:

10620

Middle Eastern (MID)

AF:

0.00685

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0247

AC:

1683

AN:

68010

Other (OTH)

AF:

0.0109

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

116

231

347

462

578

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

150

<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:

0.0216

Hom.:

Bravo

AF:

0.0131

TwinsUK

AF:

0.0218

AC:

ALSPAC

AF:

0.0195

AC:

ESP6500AA

AF:

0.00499

AC:

ESP6500EA

AF:

0.0240

AC:

206

ExAC

AF:

0.0158

AC:

1918

Asia WGS

AF:

0.00462

AC:

AN:

3478

EpiCase

AF:

0.0213

EpiControl

AF:

0.0178

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.090

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.037

T;T

Eigen

Benign

0.12

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.74

.;T

MetaRNN

Benign

0.0069

T;T

MetaSVM

Uncertain

-0.13

MutationAssessor

Benign

1.4

L;L

PhyloP100

5.1

PrimateAI

Benign

0.48

PROVEAN

Benign

-1.9

N;N

REVEL

Uncertain

0.40

Sift

Uncertain

0.0040

D;D

Sift4G

Uncertain

0.0050

D;D

Polyphen

0.10

B;B

Vest4

0.24

MPC

0.18

ClinPred

0.014

GERP RS

5.3

Varity_R

0.20

gMVP

0.43

Mutation Taster

=97/3

polymorphism (auto)

(source)

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

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over