rs2530547

Variant names:

• chr7-34658310-C-T
• rs2530547
• NM_207172.2:c.-103C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_207172.2(NPSR1):​c.-103C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.389 in 1,319,388 control chromosomes in the GnomAD database, including 105,965 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 0.48 (19759 hom., cov: 33)
  • Exomes 𝑓: 0.38 (86206 hom.)
• Consequence: NPSR1 NM_207172.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.275
• 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.727 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPSR1	NM_207172.2	c.-103C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 9	ENST00000360581.6	NP_997055.1
NPSR1	NM_207172.2	c.-103C>T		5_prime_UTR_variant	Exon 1 of 9	ENST00000360581.6	NP_997055.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPSR1	ENST00000360581.6	c.-103C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 9	1	NM_207172.2	ENSP00000353788.1
NPSR1	ENST00000360581.6	c.-103C>T		5_prime_UTR_variant	Exon 1 of 9	1	NM_207172.2	ENSP00000353788.1

Frequencies

GnomAD3 genomes AF: 0.481 AC: 73050 AN: 152012 Hom.: 19740 Cov.: 33

Gnomad AFR AF: 0.734

Gnomad AMI AF: 0.368

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.444

Gnomad EAS AF: 0.219

Gnomad SAS AF: 0.474

Gnomad FIN AF: 0.405

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.365

Gnomad OTH AF: 0.485

GnomAD4 exome AF: 0.377 AC: 439710 AN: 1167258 Hom.: 86206 Cov.: 15 AF XY: 0.380 AC XY: 222126 AN XY: 584462

African (AFR) AF: 0.753 AC: 19972 AN: 26522

American (AMR) AF: 0.409 AC: 14738 AN: 36010

Ashkenazi Jewish (ASJ) AF: 0.441 AC: 8775 AN: 19894

East Asian (EAS) AF: 0.197 AC: 7467 AN: 37850

South Asian (SAS) AF: 0.478 AC: 33107 AN: 69230

European-Finnish (FIN) AF: 0.382 AC: 18282 AN: 47868

Middle Eastern (MID) AF: 0.522 AC: 1766 AN: 3382

European-Non Finnish (NFE) AF: 0.360 AC: 315500 AN: 876672

Other (OTH) AF: 0.403 AC: 20103 AN: 49830

GnomAD4 genome AF: 0.481 AC: 73116 AN: 152130 Hom.: 19759 Cov.: 33 AF XY: 0.482 AC XY: 35832 AN XY: 74374

African (AFR) AF: 0.734 AC: 30456 AN: 41512

American (AMR) AF: 0.463 AC: 7067 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.444 AC: 1541 AN: 3470

East Asian (EAS) AF: 0.219 AC: 1130 AN: 5162

South Asian (SAS) AF: 0.474 AC: 2284 AN: 4816

European-Finnish (FIN) AF: 0.405 AC: 4292 AN: 10600

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.365 AC: 24830 AN: 67976

Other (OTH) AF: 0.487 AC: 1028 AN: 2112

Alfa AF: 0.410 Hom.: 10459

Bravo AF: 0.498

Asia WGS AF: 0.386 AC: 1341 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	12
DANN	Benign	0.86
PhyloP100		0.28
PromoterAI		0.0028	Neutral
Mutation Taster		=300/0	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: rs2530547; hg19: chr7-34697922; COSMIC: COSV62198224; COSMIC: COSV62198224;