rs1419780

Variant names:

• chr7-34780689-C-G
• rs1419780
• NM_207172.2:c.384+2124C>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.384+2124C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 152,096 control chromosomes in the GnomAD database, including 2,079 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 0.14 (2079 hom., cov: 32)
• Consequence: NPSR1 NM_207172.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0620
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.305 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPSR1	NM_207172.2	MANE Select	c.384+2124C>G		intron	N/A	NP_997055.1
	NPSR1	NM_001300935.2		c.384+2124C>G		intron	N/A	NP_001287864.1
	NPSR1	NM_207173.2		c.384+2124C>G		intron	N/A	NP_997056.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPSR1	ENST00000360581.6	TSL:1 MANE Select	c.384+2124C>G		intron	N/A	ENSP00000353788.1
	NPSR1	ENST00000381539.3	TSL:1	c.384+2124C>G		intron	N/A	ENSP00000370950.3
	NPSR1	ENST00000359791.5	TSL:1	c.384+2124C>G		intron	N/A	ENSP00000352839.1

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21839 AN: 151978 Hom.: 2079 Cov.: 32

Gnomad AFR AF: 0.0381

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.129

Gnomad EAS AF: 0.317

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.238

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.141

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

GnomAD4 genome AF: 0.144 AC: 21833 AN: 152096 Hom.: 2079 Cov.: 32 AF XY: 0.145 AC XY: 10808 AN XY: 74322

African (AFR) AF: 0.0381 AC: 1581 AN: 41546

American (AMR) AF: 0.148 AC: 2251 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.129 AC: 449 AN: 3468

East Asian (EAS) AF: 0.317 AC: 1636 AN: 5154

South Asian (SAS) AF: 0.102 AC: 492 AN: 4826

European-Finnish (FIN) AF: 0.238 AC: 2513 AN: 10566

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.183 AC: 12467 AN: 67982

Other (OTH) AF: 0.142 AC: 299 AN: 2108

Alfa AF: 0.170 Hom.: 359

Bravo AF: 0.136

Asia WGS AF: 0.187 AC: 649 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.5
DANN	Benign	0.57
PhyloP100		-0.062
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: rs1419780; hg19: chr7-34820301; COSMIC: COSV62196605; COSMIC: COSV62196605;