dbSNP rs11264580: PEAR1:p.His400His (chr1-156908739-T-C) – 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.1200T>C(p.His400His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 1,567,880 control chromosomes in the GnomAD database, including 18,492 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 0.18 ( 2615 hom., cov: 33)

Exomes 𝑓: 0.14 ( 15877 hom. )

Consequence

PEAR1
NM_001080471.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.480

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=-0.6).

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.1200T>C	p.His400His	synonymous_variant	Exon 10 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.1200T>C	p.His400His	synonymous_variant	Exon 10 of 23	5	NM_001080471.3	ENSP00000292357.7	Q5VY43
PEAR1	ENST00000338302.7 link	c.1200T>C	p.His400His	synonymous_variant	Exon 11 of 24	5		ENSP00000344465.3	Q5VY43
PEAR1	ENST00000469390.5 link	n.928T>C		non_coding_transcript_exon_variant	Exon 5 of 18	2

Frequencies

GnomAD3 genomes

AF:

0.178

AC:

26981

AN:

151960

Hom.:

2608

Cov.:

show subpopulations

Gnomad AFR

AF:

0.244

Gnomad AMI

AF:

0.133

Gnomad AMR

AF:

0.182

Gnomad ASJ

AF:

0.122

Gnomad EAS

AF:

0.335

Gnomad SAS

AF:

0.229

Gnomad FIN

AF:

0.153

Gnomad MID

AF:

0.123

Gnomad NFE

AF:

0.128

Gnomad OTH

AF:

0.162

GnomAD2 exomes

AF:

0.169

AC:

30645

AN:

181572

AF XY:

0.168

show subpopulations

Gnomad AFR exome

AF:

0.241

Gnomad AMR exome

AF:

0.177

Gnomad ASJ exome

AF:

0.118

Gnomad EAS exome

AF:

0.327

Gnomad FIN exome

AF:

0.138

Gnomad NFE exome

AF:

0.124

Gnomad OTH exome

AF:

0.156

GnomAD4 exome

AF:

0.141

AC:

199560

AN:

1415796

Hom.:

15877

Cov.:

AF XY:

0.143

AC XY:

100318

AN XY:

701494

show subpopulations

African (AFR)

AF:

0.247

AC:

7991

AN:

32346

American (AMR)

AF:

0.180

AC:

6910

AN:

38444

Ashkenazi Jewish (ASJ)

AF:

0.117

AC:

2979

AN:

25426

East Asian (EAS)

AF:

0.355

AC:

13163

AN:

37062

South Asian (SAS)

AF:

0.216

AC:

17785

AN:

82294

European-Finnish (FIN)

AF:

0.143

AC:

6302

AN:

43930

Middle Eastern (MID)

AF:

0.132

AC:

697

AN:

5272

European-Non Finnish (NFE)

AF:

0.123

AC:

134834

AN:

1092208

Other (OTH)

AF:

0.151

AC:

8899

AN:

58814

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

10335

20670

31004

41339

51674

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5140

10280

15420

20560

25700

<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:

0.178

AC:

27012

AN:

152084

Hom.:

2615

Cov.:

AF XY:

0.182

AC XY:

13519

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.244

AC:

10132

AN:

41494

American (AMR)

AF:

0.182

AC:

2780

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.122

AC:

422

AN:

3468

East Asian (EAS)

AF:

0.335

AC:

1726

AN:

5150

South Asian (SAS)

AF:

0.230

AC:

1100

AN:

4788

European-Finnish (FIN)

AF:

0.153

AC:

1619

AN:

10598

Middle Eastern (MID)

AF:

0.139

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.128

AC:

8722

AN:

67972

Other (OTH)

AF:

0.165

AC:

349

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1142

2285

3427

4570

5712

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

298

596

894

1192

1490

<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:

0.133

Hom.:

744

Bravo

AF:

0.181

Asia WGS

AF:

0.272

AC:

942

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

7.7

(source)

DANN

Benign

0.55

PhyloP100

-0.48

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