Variant 7-34849570-A-G 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.1031A>G(p.Gln344Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 1,612,262 control chromosomes in the GnomAD database, including 90,615 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/16 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.33 ( 8702 hom., cov: 33)

Exomes 𝑓: 0.33 ( 81913 hom. )

Consequence

NPSR1
NM_207172.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0880

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005805552).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPSR1	NM_207172.2 link	c.1031A>G	p.Gln344Arg	missense_variant	Exon 9 of 9	ENST00000360581.6	NP_997055.1	Q6W5P4-1A0A090N8Z1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPSR1	ENST00000360581.6 link	c.1031A>G	p.Gln344Arg	missense_variant	Exon 9 of 9	1	NM_207172.2	ENSP00000353788.1		Q6W5P4-1

Frequencies

GnomAD3 genomes

AF:

0.332

AC:

50397

AN:

152022

Hom.:

8692

Cov.:

show subpopulations

Gnomad AFR

AF:

0.384

Gnomad AMI

AF:

0.475

Gnomad AMR

AF:

0.256

Gnomad ASJ

AF:

0.338

Gnomad EAS

AF:

0.163

Gnomad SAS

AF:

0.162

Gnomad FIN

AF:

0.288

Gnomad MID

AF:

0.402

Gnomad NFE

AF:

0.345

Gnomad OTH

AF:

0.336

GnomAD3 exomes

AF:

0.283

AC:

71077

AN:

251364

Hom.:

10901

AF XY:

0.279

AC XY:

37970

AN XY:

135856

show subpopulations

Gnomad AFR exome

AF:

0.386

Gnomad AMR exome

AF:

0.180

Gnomad ASJ exome

AF:

0.341

Gnomad EAS exome

AF:

0.150

Gnomad SAS exome

AF:

0.156

Gnomad FIN exome

AF:

0.292

Gnomad NFE exome

AF:

0.347

Gnomad OTH exome

AF:

0.312

GnomAD4 exome

AF:

0.329

AC:

479727

AN:

1460122

Hom.:

81913

Cov.:

AF XY:

0.323

AC XY:

234378

AN XY:

726468

show subpopulations

Gnomad4 AFR exome

AF:

0.390

Gnomad4 AMR exome

AF:

0.190

Gnomad4 ASJ exome

AF:

0.344

Gnomad4 EAS exome

AF:

0.190

Gnomad4 SAS exome

AF:

0.161

Gnomad4 FIN exome

AF:

0.296

Gnomad4 NFE exome

AF:

0.351

Gnomad4 OTH exome

AF:

0.325

GnomAD4 genome

AF:

0.331

AC:

50434

AN:

152140

Hom.:

8702

Cov.:

AF XY:

0.323

AC XY:

24016

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.384

Gnomad4 AMR

AF:

0.255

Gnomad4 ASJ

AF:

0.338

Gnomad4 EAS

AF:

0.163

Gnomad4 SAS

AF:

0.162

Gnomad4 FIN

AF:

0.288

Gnomad4 NFE

AF:

0.345

Gnomad4 OTH

AF:

0.331

Alfa

AF:

0.340

Hom.:

18655

Bravo

AF:

0.333

TwinsUK

AF:

0.361

AC:

1340

ALSPAC

AF:

0.365

AC:

1406

ESP6500AA

AF:

0.392

AC:

1728

ESP6500EA

AF:

0.349

AC:

3005

ExAC

AF:

0.287

AC:

34796

Asia WGS

AF:

0.158

AC:

548

AN:

3478

EpiCase

AF:

0.351

EpiControl

AF:

0.343

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.056

BayesDel_addAF

Benign

-0.78

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.21

DANN

Benign

0.61

DEOGEN2

Benign

0.048

T;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0084

LIST_S2

Benign

0.28

T;T

MetaRNN

Benign

0.0058

T;T

MetaSVM

Benign

-0.91

PROVEAN

Benign

0.45

N;N

REVEL

Benign

0.025

Sift

Benign

0.87

T;T

Sift4G

Benign

0.95

T;T

Polyphen

0.0

B;B

Vest4

0.066

ClinPred

0.0067

GERP RS

-1.2

Varity_R

0.037

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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