NM_207172.2:c.281-5772G>C

Variant names:

• chr7-34772690-G-C
• rs740347
• NM_207172.2:c.281-5772G>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.281-5772G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 152,154 control chromosomes in the GnomAD database, including 1,119 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 0.11 (1119 hom., cov: 32)
• Consequence: NPSR1 NM_207172.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0400
• Publications: 13 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=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207172.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPSR1	NM_207172.2	MANE Select	c.281-5772G>C		intron	N/A	NP_997055.1
	NPSR1	NM_001300935.2		c.281-5772G>C		intron	N/A	NP_001287864.1
	NPSR1	NM_207173.2		c.281-5772G>C		intron	N/A	NP_997056.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPSR1	ENST00000360581.6	TSL:1 MANE Select	c.281-5772G>C		intron	N/A	ENSP00000353788.1
	NPSR1	ENST00000381539.3	TSL:1	c.281-5772G>C		intron	N/A	ENSP00000370950.3
	NPSR1	ENST00000359791.5	TSL:1	c.281-5772G>C		intron	N/A	ENSP00000352839.1

Frequencies

GnomAD3 genomes AF: 0.112 AC: 17102 AN: 152036 Hom.: 1119 Cov.: 32

Gnomad AFR AF: 0.0505

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.0931

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.122

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.174

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.145

Gnomad OTH AF: 0.115

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

GnomAD4 genome AF: 0.112 AC: 17101 AN: 152154 Hom.: 1119 Cov.: 32 AF XY: 0.112 AC XY: 8309 AN XY: 74394

African (AFR) AF: 0.0504 AC: 2094 AN: 41544

American (AMR) AF: 0.0929 AC: 1418 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 357 AN: 3468

East Asian (EAS) AF: 0.121 AC: 627 AN: 5164

South Asian (SAS) AF: 0.102 AC: 491 AN: 4820

European-Finnish (FIN) AF: 0.174 AC: 1842 AN: 10590

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.145 AC: 9829 AN: 67984

Other (OTH) AF: 0.113 AC: 239 AN: 2112

Alfa AF: 0.0468 Hom.: 63

Bravo AF: 0.104

Asia WGS AF: 0.110 AC: 383 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.7
DANN	Benign	0.88
PhyloP100		-0.040
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: rs740347; hg19: chr7-34812302;