ENST00000359791.5:c.1026-9902A>C

Variant names:

• chr7-34868174-A-C
• rs1833090
• ENST00000359791.5:c.1026-9902A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000359791.5(NPSR1):​c.1026-9902A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.771 in 151,388 control chromosomes in the GnomAD database, including 45,692 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 0.77 (45692 hom., cov: 30)
• Consequence: NPSR1 ENST00000359791.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.87
• Publications: 6 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.884 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000359791.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPSR1	NM_207173.2		c.1026-9902A>C		intron	N/A	NP_997056.1	Q6W5P4-4
	NPSR1	NM_001300933.2		c.993-9902A>C		intron	N/A	NP_001287862.1	Q6W5P4-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPSR1	ENST00000359791.5	TSL:1	c.1026-9902A>C		intron	N/A	ENSP00000352839.1	Q6W5P4-4
	NPSR1	ENST00000531252.5	TSL:1	c.993-9902A>C		intron	N/A	ENSP00000433258.1	Q6W5P4-5
	NPSR1-AS1	ENST00000431669.5	TSL:1	n.84+3325T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.771 AC: 116654 AN: 151268 Hom.: 45635 Cov.: 30

Gnomad AFR AF: 0.891

Gnomad AMI AF: 0.851

Gnomad AMR AF: 0.696

Gnomad ASJ AF: 0.737

Gnomad EAS AF: 0.558

Gnomad SAS AF: 0.852

Gnomad FIN AF: 0.764

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.729

Gnomad OTH AF: 0.745

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.771 AC: 116769 AN: 151388 Hom.: 45692 Cov.: 30 AF XY: 0.772 AC XY: 57101 AN XY: 73990

African (AFR) AF: 0.892 AC: 36441 AN: 40874

American (AMR) AF: 0.695 AC: 10609 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.737 AC: 2557 AN: 3470

East Asian (EAS) AF: 0.558 AC: 2868 AN: 5140

South Asian (SAS) AF: 0.853 AC: 4103 AN: 4808

European-Finnish (FIN) AF: 0.764 AC: 8077 AN: 10572

Middle Eastern (MID) AF: 0.776 AC: 228 AN: 294

European-Non Finnish (NFE) AF: 0.729 AC: 49543 AN: 67960

Other (OTH) AF: 0.747 AC: 1569 AN: 2100

Alfa AF: 0.730 Hom.: 65018

Bravo AF: 0.769

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.18
DANN	Benign	0.39
PhyloP100		-3.9
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1833090; hg19: chr7-34907786;