rs2530547

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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	c.-103C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 9	1	NM_207172.2	ENSP00000353788.1
NPSR1	ENST00000360581	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

Gnomad4 AFR exome AF: 0.753

Gnomad4 AMR exome AF: 0.409

Gnomad4 ASJ exome AF: 0.441

Gnomad4 EAS exome AF: 0.197

Gnomad4 SAS exome AF: 0.478

Gnomad4 FIN exome AF: 0.382

Gnomad4 NFE exome AF: 0.360

Gnomad4 OTH exome AF: 0.403

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

Gnomad4 AFR AF: 0.734

Gnomad4 AMR AF: 0.463

Gnomad4 ASJ AF: 0.444

Gnomad4 EAS AF: 0.219

Gnomad4 SAS AF: 0.474

Gnomad4 FIN AF: 0.405

Gnomad4 NFE AF: 0.365

Gnomad4 OTH AF: 0.487

Alfa AF: 0.405 Hom.: 8635

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

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: rs2530547; hg19: chr7-34697922; COSMIC: COSV62198224; COSMIC: COSV62198224;