rs2530548

Positions:

• chr7-34658598-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_207172.2(NPSR1):​c.147+39A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.403 in 1,591,130 control chromosomes in the GnomAD database, including 133,380 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 0.41 (13506 hom., cov: 33)
  • Exomes 𝑓: 0.40 (119874 hom.)
• Consequence: NPSR1 NM_207172.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.207

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.467 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPSR1	NM_207172.2	c.147+39A>G		intron_variant		ENST00000360581.6	NP_997055.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NPSR1	ENST00000360581.6	c.147+39A>G		intron_variant		1	NM_207172.2	ENSP00000353788.1

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62771 AN: 151926 Hom.: 13497 Cov.: 33

Gnomad AFR AF: 0.473

Gnomad AMI AF: 0.374

Gnomad AMR AF: 0.437

Gnomad ASJ AF: 0.451

Gnomad EAS AF: 0.127

Gnomad SAS AF: 0.456

Gnomad FIN AF: 0.330

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.401

Gnomad OTH AF: 0.425

GnomAD3 exomes AF: 0.392 AC: 96184 AN: 245612 Hom.: 19912 AF XY: 0.396 AC XY: 52657 AN XY: 132858

Gnomad AFR exome AF: 0.476

Gnomad AMR exome AF: 0.402

Gnomad ASJ exome AF: 0.449

Gnomad EAS exome AF: 0.114

Gnomad SAS exome AF: 0.466

Gnomad FIN exome AF: 0.325

Gnomad NFE exome AF: 0.409

Gnomad OTH exome AF: 0.409

GnomAD4 exome AF: 0.402 AC: 579019 AN: 1439086 Hom.: 119874 Cov.: 25 AF XY: 0.404 AC XY: 289754 AN XY: 716702

Gnomad4 AFR exome AF: 0.484

Gnomad4 AMR exome AF: 0.406

Gnomad4 ASJ exome AF: 0.447

Gnomad4 EAS exome AF: 0.113

Gnomad4 SAS exome AF: 0.462

Gnomad4 FIN exome AF: 0.324

Gnomad4 NFE exome AF: 0.408

Gnomad4 OTH exome AF: 0.400

GnomAD4 genome AF: 0.413 AC: 62825 AN: 152044 Hom.: 13506 Cov.: 33 AF XY: 0.411 AC XY: 30574 AN XY: 74338

Gnomad4 AFR AF: 0.472

Gnomad4 AMR AF: 0.437

Gnomad4 ASJ AF: 0.451

Gnomad4 EAS AF: 0.127

Gnomad4 SAS AF: 0.458

Gnomad4 FIN AF: 0.330

Gnomad4 NFE AF: 0.401

Gnomad4 OTH AF: 0.428

Alfa AF: 0.412 Hom.: 22057

Bravo AF: 0.423

Asia WGS AF: 0.309 AC: 1075 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.7
DANN	Benign	0.69

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

LitVar

Other links and lift over

dbSNP: rs2530548; hg19: chr7-34698210; COSMIC: COSV62201288;