7-34827512-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_207172.2(NPSR1):c.590G>T(p.Cys197Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0256 in 1,614,036 control chromosomes in the GnomAD database, including 631 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. C197W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.019 ( 37 hom., cov: 31)

Exomes 𝑓: 0.026 ( 594 hom. )

Consequence

NPSR1
NM_207172.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.01

Publications

15 publications found

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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011187613).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0188 (2865/152220) while in subpopulation NFE AF = 0.0299 (2034/68018). AF 95% confidence interval is 0.0288. There are 37 homozygotes in GnomAd4. There are 1353 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 37 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207172.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NPSR1	NM_207172.2	MANE Select	c.590G>T	p.Cys197Phe	missense	Exon 5 of 9	NP_997055.1	Q6W5P4-1
NPSR1	NM_001300935.2		c.590G>T	p.Cys197Phe	missense	Exon 5 of 10	NP_001287864.1	Q6W5P4-3
NPSR1	NM_207173.2		c.590G>T	p.Cys197Phe	missense	Exon 5 of 9	NP_997056.1	Q6W5P4-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NPSR1	ENST00000360581.6	TSL:1 MANE Select	c.590G>T	p.Cys197Phe	missense	Exon 5 of 9	ENSP00000353788.1	Q6W5P4-1
NPSR1	ENST00000381539.3	TSL:1	c.590G>T	p.Cys197Phe	missense	Exon 5 of 10	ENSP00000370950.3	Q6W5P4-3
NPSR1	ENST00000359791.5	TSL:1	c.590G>T	p.Cys197Phe	missense	Exon 5 of 9	ENSP00000352839.1	Q6W5P4-4

Frequencies

GnomAD3 genomes

AF:

0.0189

AC:

2872

AN:

152102

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00582

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0158

Gnomad ASJ

AF:

0.0210

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00871

Gnomad FIN

AF:

0.0174

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0299

Gnomad OTH

AF:

0.0206

GnomAD2 exomes

AF:

0.0208

AC:

5233

AN:

251298

AF XY:

0.0217

show subpopulations

Gnomad AFR exome

AF:

0.00461

Gnomad AMR exome

AF:

0.0152

Gnomad ASJ exome

AF:

0.0214

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0175

Gnomad NFE exome

AF:

0.0312

Gnomad OTH exome

AF:

0.0269

GnomAD4 exome

AF:

0.0264

AC:

38520

AN:

1461816

Hom.:

594

Cov.:

AF XY:

0.0260

AC XY:

18901

AN XY:

727228

show subpopulations

African (AFR)

AF:

0.00418

AC:

140

AN:

33474

American (AMR)

AF:

0.0155

AC:

693

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0198

AC:

518

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0113

AC:

972

AN:

86258

European-Finnish (FIN)

AF:

0.0178

AC:

950

AN:

53420

Middle Eastern (MID)

AF:

0.0199

AC:

115

AN:

5766

European-Non Finnish (NFE)

AF:

0.0304

AC:

33802

AN:

1111944

Other (OTH)

AF:

0.0220

AC:

1330

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

2053

4106

6159

8212

10265

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1258

2516

3774

5032

6290

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0188

AC:

2865

AN:

152220

Hom.:

Cov.:

AF XY:

0.0182

AC XY:

1353

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.00580

AC:

241

AN:

41546

American (AMR)

AF:

0.0158

AC:

241

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0210

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5166

South Asian (SAS)

AF:

0.00831

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.0174

AC:

184

AN:

10588

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0299

AC:

2034

AN:

68018

Other (OTH)

AF:

0.0204

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

136

272

408

544

680

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

160

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0261

Hom.:

273

Bravo

AF:

0.0182

TwinsUK

AF:

0.0318

AC:

118

ALSPAC

AF:

0.0275

AC:

106

ESP6500AA

AF:

0.00749

AC:

ESP6500EA

AF:

0.0298

AC:

256

ExAC

AF:

0.0217

AC:

2634

Asia WGS

AF:

0.00606

AC:

AN:

3478

EpiCase

AF:

0.0314

EpiControl

AF:

0.0316

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.98

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.11

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.58

Eigen

Pathogenic

0.89

Eigen_PC

Pathogenic

0.84

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.88

MetaRNN

Benign

0.011

MetaSVM

Uncertain

-0.28

MutationAssessor

Pathogenic

3.6

PhyloP100

7.0

PrimateAI

Uncertain

0.65

PROVEAN

Pathogenic

-10

REVEL

Uncertain

0.42

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.48

MPC

0.23

ClinPred

0.12

GERP RS

5.4

Varity_R

0.99

gMVP

0.93

Mutation Taster

=50/50

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over