chr7-34754379-A-C

Variant names:

• chr7-34754379-A-C
• rs17788770
• NM_207172.2:c.281-24083A>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.281-24083A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0751 in 152,182 control chromosomes in the GnomAD database, including 563 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 0.075 (563 hom., cov: 32)
• Consequence: NPSR1 NM_207172.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.145
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.107 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.281-24083A>C		intron	N/A	NP_997055.1	Q6W5P4-1
	NPSR1	NM_001300935.2		c.281-24083A>C		intron	N/A	NP_001287864.1	Q6W5P4-3
	NPSR1	NM_207173.2		c.281-24083A>C		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.281-24083A>C		intron	N/A	ENSP00000353788.1	Q6W5P4-1
	NPSR1	ENST00000381539.3	TSL:1	c.281-24083A>C		intron	N/A	ENSP00000370950.3	Q6W5P4-3
	NPSR1	ENST00000359791.5	TSL:1	c.281-24083A>C		intron	N/A	ENSP00000352839.1	Q6W5P4-4

Frequencies

GnomAD3 genomes AF: 0.0752 AC: 11432 AN: 152064 Hom.: 563 Cov.: 32

Gnomad AFR AF: 0.0197

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.0842

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.0568

Gnomad SAS AF: 0.0515

Gnomad FIN AF: 0.0550

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.0841

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

GnomAD4 genome AF: 0.0751 AC: 11431 AN: 152182 Hom.: 563 Cov.: 32 AF XY: 0.0735 AC XY: 5472 AN XY: 74404

African (AFR) AF: 0.0196 AC: 816 AN: 41532

American (AMR) AF: 0.0841 AC: 1285 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.133 AC: 463 AN: 3470

East Asian (EAS) AF: 0.0571 AC: 296 AN: 5182

South Asian (SAS) AF: 0.0515 AC: 248 AN: 4816

European-Finnish (FIN) AF: 0.0550 AC: 583 AN: 10598

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.109 AC: 7427 AN: 67984

Other (OTH) AF: 0.0828 AC: 175 AN: 2114

Alfa AF: 0.0890 Hom.: 210

Bravo AF: 0.0771

Asia WGS AF: 0.0430 AC: 150 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.4
DANN	Benign	0.50
PhyloP100		0.14
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: rs17788770; hg19: chr7-34793991;