rs1419779

Variant names:

• chr7-34773696-A-G
• rs1419779
• NM_207172.2:c.281-4766A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_207172.2(NPSR1):​c.281-4766A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 152,042 control chromosomes in the GnomAD database, including 7,118 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 0.30 (7118 hom., cov: 32)
• Consequence: NPSR1 NM_207172.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.481
• Publications: 3 publications found

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-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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPSR1	NM_207172.2	MANE Select	c.281-4766A>G		intron	N/A	NP_997055.1	Q6W5P4-1
	NPSR1	NM_001300935.2		c.281-4766A>G		intron	N/A	NP_001287864.1	Q6W5P4-3
	NPSR1	NM_207173.2		c.281-4766A>G		intron	N/A	NP_997056.1	Q6W5P4-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPSR1	ENST00000360581.6	TSL:1 MANE Select	c.281-4766A>G		intron	N/A	ENSP00000353788.1	Q6W5P4-1
	NPSR1	ENST00000381539.3	TSL:1	c.281-4766A>G		intron	N/A	ENSP00000370950.3	Q6W5P4-3
	NPSR1	ENST00000359791.5	TSL:1	c.281-4766A>G		intron	N/A	ENSP00000352839.1	Q6W5P4-4

Frequencies

GnomAD3 genomes AF: 0.305 AC: 46331 AN: 151924 Hom.: 7120 Cov.: 32

Gnomad AFR AF: 0.300

Gnomad AMI AF: 0.352

Gnomad AMR AF: 0.259

Gnomad ASJ AF: 0.342

Gnomad EAS AF: 0.222

Gnomad SAS AF: 0.245

Gnomad FIN AF: 0.297

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.327

Gnomad OTH AF: 0.317

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

GnomAD4 genome AF: 0.305 AC: 46334 AN: 152042 Hom.: 7118 Cov.: 32 AF XY: 0.301 AC XY: 22405 AN XY: 74324

African (AFR) AF: 0.299 AC: 12413 AN: 41482

American (AMR) AF: 0.259 AC: 3950 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.342 AC: 1189 AN: 3472

East Asian (EAS) AF: 0.222 AC: 1143 AN: 5156

South Asian (SAS) AF: 0.246 AC: 1183 AN: 4812

European-Finnish (FIN) AF: 0.297 AC: 3146 AN: 10582

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.327 AC: 22224 AN: 67960

Other (OTH) AF: 0.316 AC: 665 AN: 2104

Alfa AF: 0.318 Hom.: 33396

Bravo AF: 0.304

Asia WGS AF: 0.230 AC: 803 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.99
DANN	Benign	0.27
PhyloP100		-0.48
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1419779; hg19: chr7-34813308;