7-34670442-C-T

Variant names:

• chr7-34670442-C-T
• rs2609220
• NM_207172.2:c.147+11883C>T

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+11883C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 151,550 control chromosomes in the GnomAD database, including 8,284 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 (8284 hom., cov: 32)
• Consequence: NPSR1 NM_207172.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.222
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• 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+11883C>T		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+11883C>T		intron_variant	Intron 1 of 8	1	NM_207172.2	ENSP00000353788.1

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45474 AN: 151438 Hom.: 8272 Cov.: 32

Gnomad AFR AF: 0.522

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.215

Gnomad OTH AF: 0.302

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

GnomAD4 genome AF: 0.300 AC: 45536 AN: 151550 Hom.: 8284 Cov.: 32 AF XY: 0.297 AC XY: 22011 AN XY: 74040

African (AFR) AF: 0.522 AC: 21577 AN: 41358

American (AMR) AF: 0.200 AC: 3043 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.269 AC: 930 AN: 3462

East Asian (EAS) AF: 0.181 AC: 933 AN: 5168

South Asian (SAS) AF: 0.210 AC: 1009 AN: 4812

European-Finnish (FIN) AF: 0.243 AC: 2527 AN: 10386

Middle Eastern (MID) AF: 0.268 AC: 76 AN: 284

European-Non Finnish (NFE) AF: 0.215 AC: 14581 AN: 67848

Other (OTH) AF: 0.301 AC: 634 AN: 2104

Alfa AF: 0.233 Hom.: 2461

Bravo AF: 0.308

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.3
DANN	Benign	0.62
PhyloP100		0.22
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: rs2609220; hg19: chr7-34710054;