Variant rs28480169 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000359791.5(NPSR1):c.1040G>A(p.Arg347His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0738 in 1,598,622 control chromosomes in the GnomAD database, including 5,124 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/15 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.065 ( 453 hom., cov: 32)

Exomes 𝑓: 0.075 ( 4671 hom. )

Consequence

NPSR1
ENST00000359791.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.112

Variant links:

Genes affected

NPSR1 (HGNC:23631): (neuropeptide S receptor 1) This gene encodes a member of the vasopressin/oxytocin subfamily of G protein-coupled receptors. The encoded membrane protein acts as a receptor for neuropeptide S and affects a variety of cellular processes through its signaling. Increased expression of this gene in ciliated cells of the respiratory epithelium and in bronchial smooth muscle cells is associated with asthma. Polymorphisms in this gene have also been associated with asthma susceptibility, panic disorders, inflammatory bowel disease, and rheumatoid arthritis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

NPSR1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017320514).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0829 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPSR1	NM_207173.2 linkuse as main transcript	c.1040G>A	p.Arg347His	missense_variant	9/9
NPSR1	NM_001300933.2 linkuse as main transcript	c.1007G>A	p.Arg336His	missense_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPSR1	ENST00000359791.5 linkuse as main transcript	c.1040G>A	p.Arg347His	missense_variant	9/9	1			Q6W5P4-4
NPSR1	ENST00000531252.5 linkuse as main transcript	c.1007G>A	p.Arg336His	missense_variant	9/9	1			Q6W5P4-5

Frequencies

GnomAD3 genomes

AF:

0.0651

AC:

9904

AN:

152084

Hom.:

453

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0237

Gnomad AMI

AF:

0.205

Gnomad AMR

AF:

0.0609

Gnomad ASJ

AF:

0.166

Gnomad EAS

AF:

0.0122

Gnomad SAS

AF:

0.0570

Gnomad FIN

AF:

0.0841

Gnomad MID

AF:

0.162

Gnomad NFE

AF:

0.0848

Gnomad OTH

AF:

0.0870

GnomAD3 exomes

AF:

0.0670

AC:

16185

AN:

241456

Hom.:

689

AF XY:

0.0697

AC XY:

9068

AN XY:

130130

show subpopulations

Gnomad AFR exome

AF:

0.0208

Gnomad AMR exome

AF:

0.0449

Gnomad ASJ exome

AF:

0.162

Gnomad EAS exome

AF:

0.00189

Gnomad SAS exome

AF:

0.0556

Gnomad FIN exome

AF:

0.0825

Gnomad NFE exome

AF:

0.0821

Gnomad OTH exome

AF:

0.0815

GnomAD4 exome

AF:

0.0748

AC:

108127

AN:

1446420

Hom.:

4671

Cov.:

AF XY:

0.0755

AC XY:

54332

AN XY:

719284

show subpopulations

Gnomad4 AFR exome

AF:

0.0215

Gnomad4 AMR exome

AF:

0.0478

Gnomad4 ASJ exome

AF:

0.163

Gnomad4 EAS exome

AF:

0.0249

Gnomad4 SAS exome

AF:

0.0579

Gnomad4 FIN exome

AF:

0.0849

Gnomad4 NFE exome

AF:

0.0775

Gnomad4 OTH exome

AF:

0.0786

GnomAD4 genome

AF:

0.0650

AC:

9900

AN:

152202

Hom.:

453

Cov.:

AF XY:

0.0647

AC XY:

4812

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.0237

Gnomad4 AMR

AF:

0.0608

Gnomad4 ASJ

AF:

0.166

Gnomad4 EAS

AF:

0.0122

Gnomad4 SAS

AF:

0.0575

Gnomad4 FIN

AF:

0.0841

Gnomad4 NFE

AF:

0.0848

Gnomad4 OTH

AF:

0.0856

Alfa

AF:

0.0825

Hom.:

910

Bravo

AF:

0.0607

TwinsUK

AF:

0.0868

AC:

322

ALSPAC

AF:

0.0714

AC:

275

ESP6500AA

AF:

0.0252

AC:

111

ESP6500EA

AF:

0.0872

AC:

750

ExAC

AF:

0.0652

AC:

7917

Asia WGS

AF:

0.0300

AC:

105

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.63

CADD

Benign

7.9

DANN

Benign

0.84

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0054

LIST_S2

Benign

0.44

T;T

MetaRNN

Benign

0.0017

T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.19

PROVEAN

Benign

-0.82

N;N

REVEL

Benign

0.066

Sift

Uncertain

0.021

D;D

Sift4G

Uncertain

0.060

T;T

Polyphen

0.0

B;B

Vest4

0.0050

MPC

0.028

ClinPred

0.0016

GERP RS

0.48

Splicing

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