rs2530548

Variant names:

• chr7-34658598-A-G
• rs2530548
• NM_207172.2:c.147+39A>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.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
• Publications: 19 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 (AFR) allele frequency at 95% confidence interval = 0.467 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPSR1	NM_207172.2	c.147+39A>G		intron_variant	Intron 1 of 8	ENST00000360581.6	NP_997055.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPSR1	ENST00000360581.6	c.147+39A>G		intron_variant	Intron 1 of 8	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

GnomAD2 exomes AF: 0.392 AC: 96184 AN: 245612 AF XY: 0.396

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 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

African (AFR) AF: 0.484 AC: 15954 AN: 32996

American (AMR) AF: 0.406 AC: 18004 AN: 44312

Ashkenazi Jewish (ASJ) AF: 0.447 AC: 11442 AN: 25572

East Asian (EAS) AF: 0.113 AC: 4445 AN: 39510

South Asian (SAS) AF: 0.462 AC: 39295 AN: 85092

European-Finnish (FIN) AF: 0.324 AC: 17238 AN: 53218

Middle Eastern (MID) AF: 0.513 AC: 2933 AN: 5718

European-Non Finnish (NFE) AF: 0.408 AC: 445917 AN: 1093152

Other (OTH) AF: 0.400 AC: 23791 AN: 59516

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

African (AFR) AF: 0.472 AC: 19584 AN: 41456

American (AMR) AF: 0.437 AC: 6679 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.451 AC: 1566 AN: 3472

East Asian (EAS) AF: 0.127 AC: 660 AN: 5182

South Asian (SAS) AF: 0.458 AC: 2210 AN: 4822

European-Finnish (FIN) AF: 0.330 AC: 3482 AN: 10558

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.401 AC: 27258 AN: 67956

Other (OTH) AF: 0.428 AC: 905 AN: 2114

Alfa AF: 0.409 Hom.: 50028

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
PhyloP100		0.21
PromoterAI		0.0030	Neutral
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: rs2530548; hg19: chr7-34698210; COSMIC: COSV62201288;