rs2530566

Variant names:

• chr7-34665211-A-G
• rs2530566
• NM_207172.2:c.147+6652A>G

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+6652A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.554 in 152,022 control chromosomes in the GnomAD database, including 24,832 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 0.55 (24832 hom., cov: 32)
• Consequence: NPSR1 NM_207172.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.512
• Publications: 7 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.754 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207172.2. 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_207172.2	MANE Select	c.147+6652A>G		intron	N/A	NP_997055.1	Q6W5P4-1
	NPSR1	NM_001300935.2		c.147+6652A>G		intron	N/A	NP_001287864.1	Q6W5P4-3
	NPSR1	NM_207173.2		c.147+6652A>G		intron	N/A	NP_997056.1	Q6W5P4-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPSR1	ENST00000360581.6	TSL:1 MANE Select	c.147+6652A>G		intron	N/A	ENSP00000353788.1	Q6W5P4-1
	NPSR1	ENST00000381539.3	TSL:1	c.147+6652A>G		intron	N/A	ENSP00000370950.3	Q6W5P4-3
	NPSR1	ENST00000359791.5	TSL:1	c.147+6652A>G		intron	N/A	ENSP00000352839.1	Q6W5P4-4

Frequencies

GnomAD3 genomes AF: 0.553 AC: 84060 AN: 151904 Hom.: 24795 Cov.: 32

Gnomad AFR AF: 0.761

Gnomad AMI AF: 0.478

Gnomad AMR AF: 0.512

Gnomad ASJ AF: 0.530

Gnomad EAS AF: 0.241

Gnomad SAS AF: 0.553

Gnomad FIN AF: 0.473

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.475

Gnomad OTH AF: 0.559

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

GnomAD4 genome AF: 0.554 AC: 84151 AN: 152022 Hom.: 24832 Cov.: 32 AF XY: 0.552 AC XY: 41004 AN XY: 74324

African (AFR) AF: 0.761 AC: 31559 AN: 41480

American (AMR) AF: 0.512 AC: 7813 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.530 AC: 1840 AN: 3470

East Asian (EAS) AF: 0.241 AC: 1245 AN: 5172

South Asian (SAS) AF: 0.555 AC: 2676 AN: 4820

European-Finnish (FIN) AF: 0.473 AC: 4994 AN: 10554

Middle Eastern (MID) AF: 0.578 AC: 170 AN: 294

European-Non Finnish (NFE) AF: 0.474 AC: 32236 AN: 67938

Other (OTH) AF: 0.560 AC: 1183 AN: 2114

Alfa AF: 0.524 Hom.: 3588

Bravo AF: 0.566

Asia WGS AF: 0.438 AC: 1520 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.4
DANN	Benign	0.41
PhyloP100		-0.51
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: rs2530566; hg19: chr7-34704823;