1-156907990-G-T

Variant names:

• chr1-156907990-G-T
• rs145275734
• NM_001080471.3:c.841G>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001080471.3(PEAR1):​c.841G>T​(p.Gly281Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000942 in 1,574,882 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0050 (8 hom., cov: 32)
  • Exomes 𝑓: 0.00051 (6 hom.)
• Consequence: PEAR1 NM_001080471.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.625
• 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0150509775).
• BP6: Variant 1-156907990-G-T is Benign according to our data. Variant chr1-156907990-G-T is described in ClinVar as Benign. ClinVar VariationId is 789552.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00498 (758/152224) while in subpopulation AFR AF = 0.0174 (722/41524). AF 95% confidence interval is 0.0163. There are 8 homozygotes in GnomAd4. There are 342 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 8 AR gene

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.841G>T	p.Gly281Cys	missense	Exon 8 of 23	NP_001073940.1	Q5VY43
	PEAR1	NM_001353682.2		c.649G>T	p.Gly217Cys	missense	Exon 8 of 23	NP_001340611.1
	PEAR1	NM_001353683.2		c.649G>T	p.Gly217Cys	missense	Exon 9 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.841G>T	p.Gly281Cys	missense	Exon 8 of 23	ENSP00000292357.7	Q5VY43
	PEAR1	ENST00000971373.1		c.868G>T	p.Gly290Cys	missense	Exon 10 of 25	ENSP00000641432.1
	PEAR1	ENST00000338302.7	TSL:5	c.841G>T	p.Gly281Cys	missense	Exon 9 of 24	ENSP00000344465.3	Q5VY43

Frequencies

GnomAD3 genomes AF: 0.00498 AC: 758 AN: 152106 Hom.: 8 Cov.: 32

Gnomad AFR AF: 0.0174

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00192

GnomAD2 exomes AF: 0.00115 AC: 212 AN: 185056 AF XY: 0.000767

Gnomad AFR exome AF: 0.0177

Gnomad AMR exome AF: 0.000505

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000389

Gnomad OTH exome AF: 0.000203

GnomAD4 exome AF: 0.000510 AC: 725 AN: 1422658 Hom.: 6 Cov.: 35 AF XY: 0.000460 AC XY: 324 AN XY: 704136

African (AFR) AF: 0.0190 AC: 620 AN: 32654

American (AMR) AF: 0.000718 AC: 28 AN: 38984

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25442

East Asian (EAS) AF: 0.00 AC: 0 AN: 37528

South Asian (SAS) AF: 0.0000122 AC: 1 AN: 81818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50270

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5716

European-Non Finnish (NFE) AF: 0.0000110 AC: 12 AN: 1091376

Other (OTH) AF: 0.00109 AC: 64 AN: 58870

GnomAD4 genome AF: 0.00498 AC: 758 AN: 152224 Hom.: 8 Cov.: 32 AF XY: 0.00459 AC XY: 342 AN XY: 74442

African (AFR) AF: 0.0174 AC: 722 AN: 41524

American (AMR) AF: 0.00196 AC: 30 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68002

Other (OTH) AF: 0.00190 AC: 4 AN: 2108

Alfa AF: 0.00137 Hom.: 10

Bravo AF: 0.00574

ESP6500AA AF: 0.0135 AC: 59

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00119 AC: 143

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.29	T
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Pathogenic	0.98	D
MetaRNN	Benign	0.015	T
MetaSVM	Uncertain	0.69	D
MutationAssessor	Pathogenic	3.6	H
PhyloP100		0.63
PrimateAI	Benign	0.45	T
PROVEAN	Pathogenic	-6.8	D
REVEL	Uncertain	0.45
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.69
MVP		0.73
MPC		0.66
ClinPred		0.18	T
GERP RS		3.6
Varity_R		0.80
gMVP		0.81
Mutation Taster		=89/11	polymorphism

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

Other links and lift over

dbSNP: rs145275734; hg19: chr1-156877782; COSMIC: COSV52775117; COSMIC: COSV52775117;