7-34748564-G-C

Variant names:

• chr7-34748564-G-C
• rs324398
• NM_207172.2:c.281-29898G>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.281-29898G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.738 in 152,092 control chromosomes in the GnomAD database, including 42,659 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 0.74 (42659 hom., cov: 32)
• Consequence: NPSR1 NM_207172.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.436
• Publications: 2 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=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.923 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPSR1	NM_207172.2	c.281-29898G>C		intron_variant	Intron 2 of 8	ENST00000360581.6	NP_997055.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPSR1	ENST00000360581.6	c.281-29898G>C		intron_variant	Intron 2 of 8	1	NM_207172.2	ENSP00000353788.1

Frequencies

GnomAD3 genomes AF: 0.738 AC: 112159 AN: 151974 Hom.: 42598 Cov.: 32

Gnomad AFR AF: 0.930

Gnomad AMI AF: 0.649

Gnomad AMR AF: 0.671

Gnomad ASJ AF: 0.651

Gnomad EAS AF: 0.569

Gnomad SAS AF: 0.670

Gnomad FIN AF: 0.664

Gnomad MID AF: 0.680

Gnomad NFE AF: 0.671

Gnomad OTH AF: 0.727

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

GnomAD4 genome AF: 0.738 AC: 112282 AN: 152092 Hom.: 42659 Cov.: 32 AF XY: 0.736 AC XY: 54685 AN XY: 74324

African (AFR) AF: 0.930 AC: 38629 AN: 41518

American (AMR) AF: 0.671 AC: 10258 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.651 AC: 2255 AN: 3466

East Asian (EAS) AF: 0.569 AC: 2929 AN: 5146

South Asian (SAS) AF: 0.670 AC: 3230 AN: 4818

European-Finnish (FIN) AF: 0.664 AC: 7007 AN: 10558

Middle Eastern (MID) AF: 0.690 AC: 203 AN: 294

European-Non Finnish (NFE) AF: 0.671 AC: 45645 AN: 67978

Other (OTH) AF: 0.725 AC: 1534 AN: 2116

Alfa AF: 0.579 Hom.: 1552

Bravo AF: 0.750

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.4
DANN	Benign	0.54
PhyloP100		0.44
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: rs324398; hg19: chr7-34788176;