1-156908739-T-G

Variant names:

• chr1-156908739-T-G
• rs11264580
• NM_001080471.3:c.1200T>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.1200T>G​(p.His400Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000141 in 1,416,020 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PEAR1 NM_001080471.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.480
• Publications: 18 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=0.15640399).

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.1200T>G	p.His400Gln	missense	Exon 10 of 23	NP_001073940.1
	PEAR1	NM_001353682.2		c.1008T>G	p.His336Gln	missense	Exon 10 of 23	NP_001340611.1
	PEAR1	NM_001353683.2		c.1008T>G	p.His336Gln	missense	Exon 11 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.1200T>G	p.His400Gln	missense	Exon 10 of 23	ENSP00000292357.7
	PEAR1	ENST00000971373.1		c.1227T>G	p.His409Gln	missense	Exon 12 of 25	ENSP00000641432.1
	PEAR1	ENST00000338302.7	TSL:5	c.1200T>G	p.His400Gln	missense	Exon 11 of 24	ENSP00000344465.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000141 AC: 2 AN: 1416020 Hom.: 0 Cov.: 34 AF XY: 0.00000143 AC XY: 1 AN XY: 701646

African (AFR) AF: 0.00 AC: 0 AN: 32350

American (AMR) AF: 0.00 AC: 0 AN: 38474

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25426

East Asian (EAS) AF: 0.00 AC: 0 AN: 37070

South Asian (SAS) AF: 0.00 AC: 0 AN: 82328

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43982

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5274

European-Non Finnish (NFE) AF: 0.00000183 AC: 2 AN: 1092288

Other (OTH) AF: 0.00 AC: 0 AN: 58828

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.51
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.060	T
Eigen	Benign	-0.058
Eigen_PC	Benign	-0.14
FATHMM_MKL	Benign	0.46	N
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		-0.48
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.097
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.022	D
Polyphen		0.83	P
Vest4		0.25
MutPred		0.25		Loss of catalytic residue at H400 (P = 0.13)
MVP		0.54
MPC		0.16
ClinPred		0.96	D
GERP RS		1.9
Varity_R		0.30
gMVP		0.49
Mutation Taster		=77/23	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: rs11264580; hg19: chr1-156878531;