Genetic Variant PEAR1:c.2081-25C>T (chr1-156912469-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001080471.3(PEAR1):c.2081-25C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 1,607,396 control chromosomes in the GnomAD database, including 15,286 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 0.12 ( 1805 hom., cov: 32)

Exomes 𝑓: 0.10 ( 13481 hom. )

Consequence

PEAR1
NM_001080471.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0860

Publications

18 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.432 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	Effect	Exon Rank	Protein
PEAR1	NM_001080471.3	MANE Select	c.2081-25C>T	intron	N/A	NP_001073940.1
PEAR1	NM_001353682.2		c.1889-25C>T	intron	N/A	NP_001340611.1
PEAR1	NM_001353683.2		c.1889-25C>T	intron	N/A	NP_001340612.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PEAR1	ENST00000292357.8	TSL:5 MANE Select	c.2081-25C>T	intron	N/A	ENSP00000292357.7
PEAR1	ENST00000338302.7	TSL:5	c.2081-25C>T	intron	N/A	ENSP00000344465.3
PEAR1	ENST00000469390.5	TSL:2	n.1809-25C>T	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.125

AC:

18973

AN:

152108

Hom.:

1797

Cov.:

show subpopulations

Gnomad AFR

AF:

0.139

Gnomad AMI

AF:

0.0724

Gnomad AMR

AF:

0.231

Gnomad ASJ

AF:

0.0709

Gnomad EAS

AF:

0.447

Gnomad SAS

AF:

0.270

Gnomad FIN

AF:

0.0565

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.0719

Gnomad OTH

AF:

0.125

GnomAD2 exomes

AF:

0.166

AC:

40898

AN:

245812

AF XY:

0.161

show subpopulations

Gnomad AFR exome

AF:

0.141

Gnomad AMR exome

AF:

0.352

Gnomad ASJ exome

AF:

0.0745

Gnomad EAS exome

AF:

0.469

Gnomad FIN exome

AF:

0.0536

Gnomad NFE exome

AF:

0.0723

Gnomad OTH exome

AF:

0.131

GnomAD4 exome

AF:

0.101

AC:

147235

AN:

1455170

Hom.:

13481

Cov.:

AF XY:

0.105

AC XY:

75666

AN XY:

723400

show subpopulations

African (AFR)

AF:

0.140

AC:

4636

AN:

33166

American (AMR)

AF:

0.336

AC:

14698

AN:

43724

Ashkenazi Jewish (ASJ)

AF:

0.0728

AC:

1870

AN:

25672

East Asian (EAS)

AF:

0.449

AC:

17768

AN:

39614

South Asian (SAS)

AF:

0.250

AC:

21381

AN:

85368

European-Finnish (FIN)

AF:

0.0541

AC:

2871

AN:

53064

Middle Eastern (MID)

AF:

0.0925

AC:

529

AN:

5720

European-Non Finnish (NFE)

AF:

0.0690

AC:

76489

AN:

1108796

Other (OTH)

AF:

0.116

AC:

6993

AN:

60046

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

6859

13718

20576

27435

34294

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3298

6596

9894

13192

16490

<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:

0.125

AC:

18998

AN:

152226

Hom.:

1805

Cov.:

AF XY:

0.130

AC XY:

9661

AN XY:

74424

show subpopulations

African (AFR)

AF:

0.138

AC:

5747

AN:

41524

American (AMR)

AF:

0.232

AC:

3549

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0709

AC:

246

AN:

3472

East Asian (EAS)

AF:

0.447

AC:

2308

AN:

5160

South Asian (SAS)

AF:

0.270

AC:

1300

AN:

4816

European-Finnish (FIN)

AF:

0.0565

AC:

600

AN:

10620

Middle Eastern (MID)

AF:

0.0816

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0718

AC:

4885

AN:

68012

Other (OTH)

AF:

0.129

AC:

273

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

772

1544

2316

3088

3860

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

220

440

660

880

1100

<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:

0.0930

Hom.:

256

Bravo

AF:

0.137

Asia WGS

AF:

0.365

AC:

1268

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

3.7

(source)

DANN

Benign

0.43

PhyloP100

0.086

Mutation Taster

=100/0

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

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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

Computational scores

Splicing

Publications

Other links and lift over