chr1-156903934-C-G

Variant names:

• chr1-156903934-C-G
• rs186465653
• NM_001080471.3:c.8C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001080471.3(PEAR1):​c.8C>G​(p.Pro3Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,656 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P3L) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PEAR1 NM_001080471.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.197
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08285874).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PEAR1	NM_001080471.3	MANE Select	c.8C>G	p.Pro3Arg	missense	Exon 2 of 23	NP_001073940.1	Q5VY43
	PEAR1	NM_001353682.2		c.-331C>G		5_prime_UTR	Exon 2 of 23	NP_001340611.1
	PEAR1	NM_001353683.2		c.-331C>G		5_prime_UTR	Exon 3 of 24	NP_001340612.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PEAR1	ENST00000292357.8	TSL:5 MANE Select	c.8C>G	p.Pro3Arg	missense	Exon 2 of 23	ENSP00000292357.7	Q5VY43
	PEAR1	ENST00000971373.1		c.8C>G	p.Pro3Arg	missense	Exon 3 of 25	ENSP00000641432.1
	PEAR1	ENST00000338302.7	TSL:5	c.8C>G	p.Pro3Arg	missense	Exon 3 of 24	ENSP00000344465.3	Q5VY43

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461656 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727160

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53300

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111926

Other (OTH) AF: 0.00 AC: 0 AN: 60386

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.014	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	7.0
DANN	Benign	0.81
DEOGEN2	Benign	0.0046	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.046	D
MetaRNN	Benign	0.083	T
MetaSVM	Benign	-0.63	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		0.20
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.30	N
REVEL	Benign	0.14
Sift	Benign	0.12	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.17	B
Vest4		0.11
MutPred		0.27		Loss of glycosylation at P3 (P = 0.011)
MVP		0.36
MPC		0.16
ClinPred		0.11	T
GERP RS		2.2
Varity_R		0.074
gMVP		0.64
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs186465653; hg19: chr1-156873726;