Variant rs727162 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_207172.2(NPSR1):c.723C>G(p.Ser241Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 1,608,648 control chromosomes in the GnomAD database, including 48,112 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.25 ( 5093 hom., cov: 32)

Exomes 𝑓: 0.23 ( 43019 hom. )

Consequence

NPSR1
NM_207172.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.24

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:

NPSR1-AS1 (HGNC:22128): (NPSR1 antisense RNA 1) This gene is located within a region that has been associated with asthma susceptibility. The locus is considered non-protein-coding based on lack of protein homology and a lack of experimental support for an encoded protein. Three alternatively spliced transcript variants have been identified for this gene. [provided by RefSeq, May 2010]

NPSR1-AS1 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=0.004612893).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPSR1	NM_207172.2 linkuse as main transcript	c.723C>G	p.Ser241Arg	missense_variant	6/9	ENST00000360581.6	NP_997055.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NPSR1	ENST00000360581.6 linkuse as main transcript	c.723C>G	p.Ser241Arg	missense_variant	6/9	1	NM_207172.2	ENSP00000353788	P1	Q6W5P4-1

Frequencies

GnomAD3 genomes

AF:

0.251

AC:

38202

AN:

151994

Hom.:

5080

Cov.:

show subpopulations

Gnomad AFR

AF:

0.270

Gnomad AMI

AF:

0.128

Gnomad AMR

AF:

0.334

Gnomad ASJ

AF:

0.240

Gnomad EAS

AF:

0.330

Gnomad SAS

AF:

0.397

Gnomad FIN

AF:

0.236

Gnomad MID

AF:

0.294

Gnomad NFE

AF:

0.210

Gnomad OTH

AF:

0.245

GnomAD3 exomes

AF:

0.281

AC:

70436

AN:

250900

Hom.:

10907

AF XY:

0.282

AC XY:

38218

AN XY:

135578

show subpopulations

Gnomad AFR exome

AF:

0.269

Gnomad AMR exome

AF:

0.418

Gnomad ASJ exome

AF:

0.225

Gnomad EAS exome

AF:

0.322

Gnomad SAS exome

AF:

0.398

Gnomad FIN exome

AF:

0.226

Gnomad NFE exome

AF:

0.218

Gnomad OTH exome

AF:

0.266

GnomAD4 exome

AF:

0.234

AC:

341227

AN:

1456536

Hom.:

43019

Cov.:

AF XY:

0.239

AC XY:

173361

AN XY:

724754

show subpopulations

Gnomad4 AFR exome

AF:

0.275

Gnomad4 AMR exome

AF:

0.411

Gnomad4 ASJ exome

AF:

0.227

Gnomad4 EAS exome

AF:

0.319

Gnomad4 SAS exome

AF:

0.398

Gnomad4 FIN exome

AF:

0.222

Gnomad4 NFE exome

AF:

0.210

Gnomad4 OTH exome

AF:

0.246

GnomAD4 genome

AF:

0.251

AC:

38243

AN:

152112

Hom.:

5093

Cov.:

AF XY:

0.259

AC XY:

19232

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.270

Gnomad4 AMR

AF:

0.334

Gnomad4 ASJ

AF:

0.240

Gnomad4 EAS

AF:

0.330

Gnomad4 SAS

AF:

0.397

Gnomad4 FIN

AF:

0.236

Gnomad4 NFE

AF:

0.210

Gnomad4 OTH

AF:

0.248

Alfa

AF:

0.185

Hom.:

977

Bravo

AF:

0.259

TwinsUK

AF:

0.203

AC:

752

ALSPAC

AF:

0.204

AC:

788

ESP6500AA

AF:

0.268

AC:

1179

ESP6500EA

AF:

0.211

AC:

1812

ExAC

AF:

0.278

AC:

33717

Asia WGS

AF:

0.370

AC:

1287

AN:

3478

EpiCase

AF:

0.216

EpiControl

AF:

0.220

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.63

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.40

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

T;.;.;.;.

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.86

D;D;D;D;D

MetaRNN

Benign

0.0046

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

L;.;L;.;L

MutationTaster

Benign

0.0023

P;P;P;P;P

PrimateAI

Uncertain

0.49

PROVEAN

Uncertain

-2.7

D;N;D;D;D

REVEL

Benign

0.077

Sift

Benign

0.049

D;T;D;T;D

Sift4G

Benign

0.43

T;T;T;T;T

Polyphen

1.0

D;D;D;D;D

Vest4

0.28

MutPred

0.28

Gain of MoRF binding (P = 0.0451);.;Gain of MoRF binding (P = 0.0451);.;Gain of MoRF binding (P = 0.0451);

MPC

0.17

ClinPred

0.018

GERP RS

4.8

Varity_R

0.31

gMVP

0.64

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

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