rs2530571

Positions:

• chr7-34670968-G-A

Variant summary

Our verdict is Benign. Variant got -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

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=-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/exons	MANE	Protein	UniProt
NPSR1	NM_207172.2	c.147+12409G>A		intron_variant		ENST00000360581.6	NP_997055.1
NPSR1-AS1	NR_033665.1	n.279+57769C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NPSR1	ENST00000360581.6	c.147+12409G>A		intron_variant		1	NM_207172.2	ENSP00000353788	P1
NPSR1-AS1	ENST00000419766.5	n.241+57769C>T		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.749

Gnomad4 AMR AF: 0.493

Gnomad4 ASJ AF: 0.449

Gnomad4 EAS AF: 0.237

Gnomad4 SAS AF: 0.541

Gnomad4 FIN AF: 0.463

Gnomad4 NFE AF: 0.447

Gnomad4 OTH AF: 0.534

Alfa AF: 0.478 Hom.: 6852

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
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs2530571; hg19: chr7-34710580;