rs324987

Positions:

• chr7-34781816-T-C
• chr7-34781816-T-G

Variant summary

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

The NM_207172.2(NPSR1):​c.384+3251T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.472 in 151,950 control chromosomes in the GnomAD database, including 17,298 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 0.47 (17298 hom., cov: 32)
• Consequence: NPSR1 NM_207172.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.634

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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.535 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPSR1	NM_207172.2	c.384+3251T>C		intron_variant		ENST00000360581.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPSR1	ENST00000360581.6	c.384+3251T>C		intron_variant		1	NM_207172.2	P1

Frequencies

GnomAD3 genomes AF: 0.472 AC: 71710 AN: 151834 Hom.: 17290 Cov.: 32

Gnomad AFR AF: 0.541

Gnomad AMI AF: 0.439

Gnomad AMR AF: 0.386

Gnomad ASJ AF: 0.429

Gnomad EAS AF: 0.540

Gnomad SAS AF: 0.337

Gnomad FIN AF: 0.487

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.455

Gnomad OTH AF: 0.461

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

GnomAD4 genome AF: 0.472 AC: 71749 AN: 151950 Hom.: 17298 Cov.: 32 AF XY: 0.470 AC XY: 34865 AN XY: 74246

Gnomad4 AFR AF: 0.541

Gnomad4 AMR AF: 0.385

Gnomad4 ASJ AF: 0.429

Gnomad4 EAS AF: 0.541

Gnomad4 SAS AF: 0.336

Gnomad4 FIN AF: 0.487

Gnomad4 NFE AF: 0.455

Gnomad4 OTH AF: 0.460

Alfa AF: 0.450 Hom.: 23337

Bravo AF: 0.473

Asia WGS AF: 0.426 AC: 1481 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.5
DANN	Benign	0.63

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: rs324987; hg19: chr7-34821428;