7-34701550-A-G

Variant names:

• chr7-34701550-A-G
• rs10259175
• NM_207172.2:c.280+16866A>G

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+16866A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.388 in 151,998 control chromosomes in the GnomAD database, including 12,233 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 0.39 (12233 hom., cov: 32)
• Consequence: NPSR1 NM_207172.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.434
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.516 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.280+16866A>G		intron	N/A	NP_997055.1
	NPSR1	NM_001300935.2		c.280+16866A>G		intron	N/A	NP_001287864.1
	NPSR1	NM_207173.2		c.280+16866A>G		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.280+16866A>G		intron	N/A	ENSP00000353788.1
	NPSR1	ENST00000381539.3	TSL:1	c.280+16866A>G		intron	N/A	ENSP00000370950.3
	NPSR1	ENST00000359791.5	TSL:1	c.280+16866A>G		intron	N/A	ENSP00000352839.1

Frequencies

GnomAD3 genomes AF: 0.388 AC: 58942 AN: 151880 Hom.: 12215 Cov.: 32

Gnomad AFR AF: 0.522

Gnomad AMI AF: 0.291

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.252

Gnomad EAS AF: 0.448

Gnomad SAS AF: 0.224

Gnomad FIN AF: 0.416

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.342

Gnomad OTH AF: 0.369

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

GnomAD4 genome AF: 0.388 AC: 59003 AN: 151998 Hom.: 12233 Cov.: 32 AF XY: 0.385 AC XY: 28578 AN XY: 74310

African (AFR) AF: 0.522 AC: 21628 AN: 41430

American (AMR) AF: 0.283 AC: 4324 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.252 AC: 875 AN: 3470

East Asian (EAS) AF: 0.448 AC: 2308 AN: 5152

South Asian (SAS) AF: 0.223 AC: 1075 AN: 4824

European-Finnish (FIN) AF: 0.416 AC: 4403 AN: 10576

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.342 AC: 23250 AN: 67942

Other (OTH) AF: 0.366 AC: 773 AN: 2110

Alfa AF: 0.266 Hom.: 814

Bravo AF: 0.389

Asia WGS AF: 0.336 AC: 1171 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.1
DANN	Benign	0.54
PhyloP100		0.43
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: rs10259175; hg19: chr7-34741162;