7-34666794-A-C

Variant names:

• chr7-34666794-A-C
• rs2609224
• NM_207172.2:c.147+8235A>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.147+8235A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 151,836 control chromosomes in the GnomAD database, including 8,446 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 0.30 (8446 hom., cov: 31)
• Consequence: NPSR1 NM_207172.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.162
• Publications: 5 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.516 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPSR1	NM_207172.2	c.147+8235A>C		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+8235A>C		intron_variant	Intron 1 of 8	1	NM_207172.2	ENSP00000353788.1

Frequencies

GnomAD3 genomes AF: 0.304 AC: 46129 AN: 151718 Hom.: 8434 Cov.: 31

Gnomad AFR AF: 0.522

Gnomad AMI AF: 0.246

Gnomad AMR AF: 0.203

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.183

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.248

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.221

Gnomad OTH AF: 0.306

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

GnomAD4 genome AF: 0.304 AC: 46190 AN: 151836 Hom.: 8446 Cov.: 31 AF XY: 0.301 AC XY: 22331 AN XY: 74200

African (AFR) AF: 0.522 AC: 21598 AN: 41358

American (AMR) AF: 0.202 AC: 3088 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.276 AC: 956 AN: 3462

East Asian (EAS) AF: 0.183 AC: 943 AN: 5146

South Asian (SAS) AF: 0.216 AC: 1038 AN: 4812

European-Finnish (FIN) AF: 0.248 AC: 2613 AN: 10530

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.221 AC: 15003 AN: 67958

Other (OTH) AF: 0.305 AC: 644 AN: 2112

Alfa AF: 0.223 Hom.: 4594

Bravo AF: 0.312

Asia WGS AF: 0.211 AC: 732 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	4.7
DANN	Benign	0.78
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: rs2609224; hg19: chr7-34706406;