rs1419837

Variant names:

• chr7-34685927-C-T
• rs1419837
• ENST00000465305.5:c.*172C>T

Variant summary

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

The ENST00000465305.5(NPSR1):​c.*172C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 232,972 control chromosomes in the GnomAD database, including 3,993 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 0.18 (3470 hom., cov: 32)
  • Exomes 𝑓: 0.12 (523 hom.)
• Consequence: NPSR1 ENST00000465305.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.357 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPSR1	NM_207172.2	c.280+1243C>T		intron_variant	Intron 2 of 8	ENST00000360581.6	NP_997055.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPSR1	ENST00000360581.6	c.280+1243C>T		intron_variant	Intron 2 of 8	1	NM_207172.2	ENSP00000353788.1

Frequencies

GnomAD3 genomes AF: 0.177 AC: 26847 AN: 151900 Hom.: 3465 Cov.: 32

Gnomad AFR AF: 0.362

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.0896

Gnomad ASJ AF: 0.0866

Gnomad EAS AF: 0.114

Gnomad SAS AF: 0.0875

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.158

GnomAD4 exome AF: 0.116 AC: 9378 AN: 80954 Hom.: 523 Cov.: 0 AF XY: 0.115 AC XY: 5134 AN XY: 44800

Gnomad4 AFR exome AF: 0.354

Gnomad4 AMR exome AF: 0.0709

Gnomad4 ASJ exome AF: 0.103

Gnomad4 EAS exome AF: 0.118

Gnomad4 SAS exome AF: 0.0989

Gnomad4 FIN exome AF: 0.174

Gnomad4 NFE exome AF: 0.117

Gnomad4 OTH exome AF: 0.130

GnomAD4 genome AF: 0.177 AC: 26885 AN: 152018 Hom.: 3470 Cov.: 32 AF XY: 0.175 AC XY: 12980 AN XY: 74312

Gnomad4 AFR AF: 0.362

Gnomad4 AMR AF: 0.0894

Gnomad4 ASJ AF: 0.0866

Gnomad4 EAS AF: 0.114

Gnomad4 SAS AF: 0.0871

Gnomad4 FIN AF: 0.156

Gnomad4 NFE AF: 0.104

Gnomad4 OTH AF: 0.156

Alfa AF: 0.120 Hom.: 649

Bravo AF: 0.181

Asia WGS AF: 0.124 AC: 429 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.25
DANN	Benign	0.43

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: rs1419837; hg19: chr7-34725539;