Variant 7-34778501-A-T 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.320A>T(p.Asn107Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.45 in 1,609,296 control chromosomes in the GnomAD database, including 165,204 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as risk factor (no stars).

Frequency

Genomes: 𝑓 0.47 ( 17297 hom., cov: 32)

Exomes 𝑓: 0.45 ( 147907 hom. )

Consequence

NPSR1
NM_207172.2 missense

Scores

Clinical Significance

risk factor no assertion criteria provided O:1

Conservation

PhyloP100: 3.31

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=5.916357E-4).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.534 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPSR1	NM_207172.2 linkuse as main transcript	c.320A>T	p.Asn107Ile	missense_variant	3/9	ENST00000360581.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPSR1	ENST00000360581.6 linkuse as main transcript	c.320A>T	p.Asn107Ile	missense_variant	3/9	1	NM_207172.2	P1	Q6W5P4-1

Frequencies

GnomAD3 genomes

AF:

0.472

AC:

71686

AN:

151878

Hom.:

17289

Cov.:

show subpopulations

Gnomad AFR

AF:

0.541

Gnomad AMI

AF:

0.437

Gnomad AMR

AF:

0.385

Gnomad ASJ

AF:

0.428

Gnomad EAS

AF:

0.541

Gnomad SAS

AF:

0.337

Gnomad FIN

AF:

0.487

Gnomad MID

AF:

0.424

Gnomad NFE

AF:

0.455

Gnomad OTH

AF:

0.460

GnomAD3 exomes

AF:

0.437

AC:

109388

AN:

250250

Hom.:

24719

AF XY:

0.432

AC XY:

58461

AN XY:

135292

show subpopulations

Gnomad AFR exome

AF:

0.543

Gnomad AMR exome

AF:

0.340

Gnomad ASJ exome

AF:

0.433

Gnomad EAS exome

AF:

0.528

Gnomad SAS exome

AF:

0.330

Gnomad FIN exome

AF:

0.475

Gnomad NFE exome

AF:

0.459

Gnomad OTH exome

AF:

0.432

GnomAD4 exome

AF:

0.447

AC:

651975

AN:

1457300

Hom.:

147907

Cov.:

AF XY:

0.444

AC XY:

322307

AN XY:

725206

show subpopulations

Gnomad4 AFR exome

AF:

0.545

Gnomad4 AMR exome

AF:

0.345

Gnomad4 ASJ exome

AF:

0.430

Gnomad4 EAS exome

AF:

0.531

Gnomad4 SAS exome

AF:

0.331

Gnomad4 FIN exome

AF:

0.473

Gnomad4 NFE exome

AF:

0.454

Gnomad4 OTH exome

AF:

0.445

GnomAD4 genome

AF:

0.472

AC:

71726

AN:

151996

Hom.:

17297

Cov.:

AF XY:

0.469

AC XY:

34855

AN XY:

74274

show subpopulations

Gnomad4 AFR

AF:

0.540

Gnomad4 AMR

AF:

0.384

Gnomad4 ASJ

AF:

0.428

Gnomad4 EAS

AF:

0.541

Gnomad4 SAS

AF:

0.337

Gnomad4 FIN

AF:

0.487

Gnomad4 NFE

AF:

0.455

Gnomad4 OTH

AF:

0.459

Alfa

AF:

0.455

Hom.:

12295

Bravo

AF:

0.473

TwinsUK

AF:

0.446

AC:

1652

ALSPAC

AF:

0.457

AC:

1762

ESP6500AA

AF:

0.546

AC:

2407

ESP6500EA

AF:

0.461

AC:

3962

ExAC

AF:

0.446

AC:

54088

Asia WGS

AF:

0.425

AC:

1477

AN:

3478

EpiCase

AF:

0.452

EpiControl

AF:

0.452

ClinVar

Significance: risk factor

Submissions summary: Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Asthma-related traits, susceptibility to, 2

Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Apr 09, 2004

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.021

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.77

DEOGEN2

Benign

0.048

.;T;.;.;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.068

T;T;T;T;T

MetaRNN

Benign

0.00059

T;T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-2.5

N;N;N;.;N

MutationTaster

Benign

1.0

P;P;P;P;P;P

PrimateAI

Uncertain

0.75

PROVEAN

Benign

5.7

N;N;N;N;N

REVEL

Benign

0.12

Sift

Benign

1.0

T;T;T;T;T

Sift4G

Benign

1.0

T;T;T;T;T

Polyphen

0.0

.;B;B;B;B

Vest4

0.10

MPC

0.027

ClinPred

0.0047

GERP RS

5.1

Varity_R

0.15

gMVP

0.10

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over