rs1419837

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.357 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000465305.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPSR1	NM_207172.2	MANE Select	c.280+1243C>T		intron	N/A	NP_997055.1
	NPSR1	NM_001300935.2		c.280+1243C>T		intron	N/A	NP_001287864.1
	NPSR1	NM_207173.2		c.280+1243C>T		intron	N/A	NP_997056.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPSR1	ENST00000465305.5	TSL:1	c.*172C>T		3_prime_UTR	Exon 3 of 3	ENSP00000434955.1
	NPSR1	ENST00000360581.6	TSL:1 MANE Select	c.280+1243C>T		intron	N/A	ENSP00000353788.1
	NPSR1	ENST00000381539.3	TSL:1	c.280+1243C>T		intron	N/A	ENSP00000370950.3

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

African (AFR) AF: 0.354 AC: 186 AN: 526

American (AMR) AF: 0.0709 AC: 212 AN: 2992

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 140 AN: 1354

East Asian (EAS) AF: 0.118 AC: 102 AN: 862

South Asian (SAS) AF: 0.0989 AC: 1678 AN: 16962

European-Finnish (FIN) AF: 0.174 AC: 805 AN: 4632

Middle Eastern (MID) AF: 0.0817 AC: 158 AN: 1934

European-Non Finnish (NFE) AF: 0.117 AC: 5552 AN: 47492

Other (OTH) AF: 0.130 AC: 545 AN: 4200

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

African (AFR) AF: 0.362 AC: 14999 AN: 41412

American (AMR) AF: 0.0894 AC: 1366 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0866 AC: 300 AN: 3466

East Asian (EAS) AF: 0.114 AC: 588 AN: 5172

South Asian (SAS) AF: 0.0871 AC: 420 AN: 4820

European-Finnish (FIN) AF: 0.156 AC: 1649 AN: 10568

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.104 AC: 7104 AN: 67984

Other (OTH) AF: 0.156 AC: 328 AN: 2106

Alfa AF: 0.118 Hom.: 702

Bravo AF: 0.181

Asia WGS AF: 0.124 AC: 429 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.25
DANN	Benign	0.43
PhyloP100		-1.2
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: rs1419837; hg19: chr7-34725539;