NM_207172.2:c.479-7024G>C

Variant names:

• chr7-34820377-G-C
• rs10263447
• NM_207172.2:c.479-7024G>C

Variant summary

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

The NM_207172.2(NPSR1):​c.479-7024G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 152,108 control chromosomes in the GnomAD database, including 2,074 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 0.14 (2074 hom., cov: 32)
• Consequence: NPSR1 NM_207172.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.163
• Publications: 3 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]

ENSG00000300889 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPSR1	NM_207172.2	c.479-7024G>C		intron_variant	Intron 4 of 8	ENST00000360581.6	NP_997055.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPSR1	ENST00000360581.6	c.479-7024G>C		intron_variant	Intron 4 of 8	1	NM_207172.2	ENSP00000353788.1

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21833 AN: 151992 Hom.: 2074 Cov.: 32

Gnomad AFR AF: 0.0387

Gnomad AMI AF: 0.117

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.129

Gnomad EAS AF: 0.318

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.237

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.140

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

GnomAD4 genome AF: 0.144 AC: 21830 AN: 152108 Hom.: 2074 Cov.: 32 AF XY: 0.145 AC XY: 10801 AN XY: 74332

African (AFR) AF: 0.0387 AC: 1606 AN: 41546

American (AMR) AF: 0.144 AC: 2196 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.129 AC: 448 AN: 3464

East Asian (EAS) AF: 0.318 AC: 1642 AN: 5158

South Asian (SAS) AF: 0.100 AC: 483 AN: 4818

European-Finnish (FIN) AF: 0.237 AC: 2505 AN: 10570

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.184 AC: 12506 AN: 67964

Other (OTH) AF: 0.142 AC: 299 AN: 2112

Alfa AF: 0.171 Hom.: 326

Bravo AF: 0.136

Asia WGS AF: 0.188 AC: 652 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.9
DANN	Benign	0.68
PhyloP100		-0.16
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: rs10263447; hg19: chr7-34859989;