Variant rs41299597 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

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. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

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

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 made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

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

BP6

Variant 1-156912965-C-G is Benign according to our data. Variant chr1-156912965-C-G is described in Lovd as [Benign].

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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 31 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PEAR1	NM_001080471.3 link	c.2405C>G	p.Ser802Cys	missense_variant	18/23	ENST00000292357.8	NP_001073940.1	Q5VY43

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PEAR1	ENST00000292357.8 link	c.2405C>G	p.Ser802Cys	missense_variant	18/23	5	NM_001080471.3	ENSP00000292357.7	Q5VY43
PEAR1	ENST00000338302.7 link	c.2405C>G	p.Ser802Cys	missense_variant	19/24	5		ENSP00000344465.3	Q5VY43
PEAR1	ENST00000469390.5 link	n.2133C>G		non_coding_transcript_exon_variant	13/18	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

GnomAD3 exomes

AF:

0.0155

AC:

3888

AN:

251172

Hom.:

AF XY:

0.0164

AC XY:

2226

AN XY:

135812

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 SAS exome

AF:

0.0170

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

Gnomad4 AFR exome

AF:

0.00338

Gnomad4 AMR exome

AF:

0.00458

Gnomad4 ASJ exome

AF:

0.0126

Gnomad4 EAS exome

AF:

0.000353

Gnomad4 SAS exome

AF:

0.0189

Gnomad4 FIN exome

AF:

0.0164

Gnomad4 NFE exome

AF:

0.0228

Gnomad4 OTH exome

AF:

0.0181

GnomAD4 genome

AF:

0.0148

AC:

2250

AN:

152278

Hom.:

Cov.:

AF XY:

0.0141

AC XY:

1051

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.00370

Gnomad4 AMR

AF:

0.00530

Gnomad4 ASJ

AF:

0.0141

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.0162

Gnomad4 FIN

AF:

0.0147

Gnomad4 NFE

AF:

0.0247

Gnomad4 OTH

AF:

0.0109

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

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

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over