rs2530571

Variant names:

• chr7-34670968-G-A
• rs2530571
• NM_207172.2:c.147+12409G>A

Variant summary

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

The NM_207172.2(NPSR1):​c.147+12409G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.533 in 151,696 control chromosomes in the GnomAD database, including 23,094 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 0.53 (23094 hom., cov: 32)
• Consequence: NPSR1 NM_207172.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.159
• Publications: 4 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 = 0.742 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPSR1	NM_207172.2	c.147+12409G>A		intron_variant	Intron 1 of 8	ENST00000360581.6	NP_997055.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPSR1	ENST00000360581.6	c.147+12409G>A		intron_variant	Intron 1 of 8	1	NM_207172.2	ENSP00000353788.1

Frequencies

GnomAD3 genomes AF: 0.532 AC: 80696 AN: 151578 Hom.: 23060 Cov.: 32

Gnomad AFR AF: 0.749

Gnomad AMI AF: 0.460

Gnomad AMR AF: 0.493

Gnomad ASJ AF: 0.449

Gnomad EAS AF: 0.237

Gnomad SAS AF: 0.538

Gnomad FIN AF: 0.463

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.447

Gnomad OTH AF: 0.533

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

GnomAD4 genome AF: 0.533 AC: 80784 AN: 151696 Hom.: 23094 Cov.: 32 AF XY: 0.533 AC XY: 39490 AN XY: 74120

African (AFR) AF: 0.749 AC: 30971 AN: 41348

American (AMR) AF: 0.493 AC: 7510 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.449 AC: 1556 AN: 3464

East Asian (EAS) AF: 0.237 AC: 1224 AN: 5166

South Asian (SAS) AF: 0.541 AC: 2603 AN: 4814

European-Finnish (FIN) AF: 0.463 AC: 4867 AN: 10506

Middle Eastern (MID) AF: 0.510 AC: 147 AN: 288

European-Non Finnish (NFE) AF: 0.447 AC: 30360 AN: 67854

Other (OTH) AF: 0.534 AC: 1127 AN: 2110

Alfa AF: 0.479 Hom.: 7829

Bravo AF: 0.545

Asia WGS AF: 0.427 AC: 1469 AN: 3448

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.9
DANN	Benign	0.26
PhyloP100		0.16
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs2530571; hg19: chr7-34710580;