Genetic Variant NPSR1:c.1026-12882G>C (chr7-34865194-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_207173.2(NPSR1):c.1026-12882G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 151,642 control chromosomes in the GnomAD database, including 4,553 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.

Frequency

Genomes: 𝑓 0.23 ( 4553 hom., cov: 32)

Consequence

NPSR1
NM_207173.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.00800

Publications

2 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:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.454 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207173.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPSR1	NM_207173.2		c.1026-12882G>C		intron	N/A	NP_997056.1	Q6W5P4-4
	NPSR1	NM_001300933.2		c.993-12882G>C		intron	N/A	NP_001287862.1	Q6W5P4-5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NPSR1	ENST00000359791.5	TSL:1	c.1026-12882G>C	intron	N/A	ENSP00000352839.1	Q6W5P4-4
NPSR1	ENST00000531252.5	TSL:1	c.993-12882G>C	intron	N/A	ENSP00000433258.1	Q6W5P4-5
NPSR1-AS1	ENST00000431669.5	TSL:1	n.84+6305C>G	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.231

AC:

35062

AN:

151524

Hom.:

4542

Cov.:

show subpopulations

Gnomad AFR

AF:

0.195

Gnomad AMI

AF:

0.138

Gnomad AMR

AF:

0.293

Gnomad ASJ

AF:

0.271

Gnomad EAS

AF:

0.296

Gnomad SAS

AF:

0.470

Gnomad FIN

AF:

0.242

Gnomad MID

AF:

0.285

Gnomad NFE

AF:

0.215

Gnomad OTH

AF:

0.228

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.231

AC:

35105

AN:

151642

Hom.:

4553

Cov.:

AF XY:

0.240

AC XY:

17821

AN XY:

74110

show subpopulations

African (AFR)

AF:

0.196

AC:

8022

AN:

41032

American (AMR)

AF:

0.293

AC:

4475

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.271

AC:

941

AN:

3472

East Asian (EAS)

AF:

0.296

AC:

1530

AN:

5170

South Asian (SAS)

AF:

0.471

AC:

2265

AN:

4814

European-Finnish (FIN)

AF:

0.242

AC:

2558

AN:

10582

Middle Eastern (MID)

AF:

0.276

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.215

AC:

14614

AN:

67984

Other (OTH)

AF:

0.234

AC:

493

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1344

2688

4032

5376

6720

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

370

740

1110

1480

1850

<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:

0.215

Hom.:

482

Bravo

AF:

0.225

Asia WGS

AF:

0.399

AC:

1384

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

1.5

(source)

DANN

Benign

0.36

PhyloP100

-0.0080

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over