1-156907617-G-T

Variant names:

• chr1-156907617-G-T
• rs773757499
• NM_001080471.3:c.652G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001080471.3(PEAR1):​c.652G>T​(p.Val218Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000754 in 1,459,812 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/24 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. V218M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000075 (0 hom.)
• Consequence: PEAR1 NM_001080471.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.137
• Publications: 4 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.029413015).

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.652G>T	p.Val218Leu	missense	Exon 7 of 23	NP_001073940.1	Q5VY43
	PEAR1	NM_001353682.2		c.460G>T	p.Val154Leu	missense	Exon 7 of 23	NP_001340611.1
	PEAR1	NM_001353683.2		c.460G>T	p.Val154Leu	missense	Exon 8 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.652G>T	p.Val218Leu	missense	Exon 7 of 23	ENSP00000292357.7	Q5VY43
	PEAR1	ENST00000971373.1		c.679G>T	p.Val227Leu	missense	Exon 9 of 25	ENSP00000641432.1
	PEAR1	ENST00000338302.7	TSL:5	c.652G>T	p.Val218Leu	missense	Exon 8 of 24	ENSP00000344465.3	Q5VY43

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000120 AC: 3 AN: 249244 AF XY: 0.00000742

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000547

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000754 AC: 11 AN: 1459812 Hom.: 0 Cov.: 30 AF XY: 0.00000826 AC XY: 6 AN XY: 726220

African (AFR) AF: 0.00 AC: 0 AN: 33406

American (AMR) AF: 0.00 AC: 0 AN: 44316

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25996

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39690

South Asian (SAS) AF: 0.000116 AC: 10 AN: 85944

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53386

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111054

Other (OTH) AF: 0.00 AC: 0 AN: 60266

GnomAD4 genome Cov.: 33

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	6.4
DANN	Benign	0.80
DEOGEN2	Benign	0.0053	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.0088	T
MetaRNN	Benign	0.029	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.15	N
PhyloP100		0.14
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.78	N
REVEL	Benign	0.026
Sift	Benign	0.45	T
Sift4G	Benign	0.44	T
Polyphen		0.0020	B
Vest4		0.063
MutPred		0.24		Loss of glycosylation at S215 (P = 0.1384)
MVP		0.25
MPC		0.15
ClinPred		0.010	T
GERP RS		0.28
Varity_R		0.030
gMVP		0.11
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.20		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.20		Position offset: 15

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

Other links and lift over

dbSNP: rs773757499; hg19: chr1-156877409;