chr7-34716363-C-A

Variant names:

• chr7-34716363-C-A
• rs324377
• NM_207172.2:c.280+31679C>A

Variant summary

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

The NM_207172.2(NPSR1):​c.280+31679C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.469 in 151,956 control chromosomes in the GnomAD database, including 17,321 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 0.47 (17321 hom., cov: 32)
• Consequence: NPSR1 NM_207172.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.439
• Publications: 11 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.582 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPSR1	NM_207172.2	MANE Select	c.280+31679C>A		intron	N/A	NP_997055.1	Q6W5P4-1
	NPSR1	NM_001300935.2		c.280+31679C>A		intron	N/A	NP_001287864.1	Q6W5P4-3
	NPSR1	NM_207173.2		c.280+31679C>A		intron	N/A	NP_997056.1	Q6W5P4-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPSR1	ENST00000360581.6	TSL:1 MANE Select	c.280+31679C>A		intron	N/A	ENSP00000353788.1	Q6W5P4-1
	NPSR1	ENST00000381539.3	TSL:1	c.280+31679C>A		intron	N/A	ENSP00000370950.3	Q6W5P4-3
	NPSR1	ENST00000359791.5	TSL:1	c.280+31679C>A		intron	N/A	ENSP00000352839.1	Q6W5P4-4

Frequencies

GnomAD3 genomes AF: 0.469 AC: 71180 AN: 151836 Hom.: 17285 Cov.: 32

Gnomad AFR AF: 0.587

Gnomad AMI AF: 0.368

Gnomad AMR AF: 0.359

Gnomad ASJ AF: 0.363

Gnomad EAS AF: 0.508

Gnomad SAS AF: 0.319

Gnomad FIN AF: 0.492

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.433

Gnomad OTH AF: 0.454

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

GnomAD4 genome AF: 0.469 AC: 71262 AN: 151956 Hom.: 17321 Cov.: 32 AF XY: 0.464 AC XY: 34457 AN XY: 74280

African (AFR) AF: 0.588 AC: 24371 AN: 41454

American (AMR) AF: 0.359 AC: 5476 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.363 AC: 1259 AN: 3464

East Asian (EAS) AF: 0.508 AC: 2613 AN: 5146

South Asian (SAS) AF: 0.318 AC: 1532 AN: 4814

European-Finnish (FIN) AF: 0.492 AC: 5189 AN: 10538

Middle Eastern (MID) AF: 0.394 AC: 115 AN: 292

European-Non Finnish (NFE) AF: 0.433 AC: 29416 AN: 67958

Other (OTH) AF: 0.452 AC: 956 AN: 2114

Alfa AF: 0.303 Hom.: 961

Bravo AF: 0.468

Asia WGS AF: 0.413 AC: 1437 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.1
DANN	Benign	0.71
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: rs324377; hg19: chr7-34755975;