7-34746786-G-T

Variant names:

• chr7-34746786-G-T
• rs10270663
• NM_207172.2:c.281-31676G>T

Variant summary

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

The NM_001300935.2(NPSR1):​c.281-31676G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.303 in 151,970 control chromosomes in the GnomAD database, including 7,505 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 (7505 hom., cov: 31)
• Consequence: NPSR1 NM_001300935.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.152
• Publications: 4 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 (EAS) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001300935.2. 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.281-31676G>T		intron	N/A	NP_997055.1
	NPSR1	NM_001300935.2		c.281-31676G>T		intron	N/A	NP_001287864.1
	NPSR1	NM_207173.2		c.281-31676G>T		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.281-31676G>T		intron	N/A	ENSP00000353788.1
	NPSR1	ENST00000381539.3	TSL:1	c.281-31676G>T		intron	N/A	ENSP00000370950.3
	NPSR1	ENST00000359791.5	TSL:1	c.281-31676G>T		intron	N/A	ENSP00000352839.1

Frequencies

GnomAD3 genomes AF: 0.303 AC: 46078 AN: 151852 Hom.: 7504 Cov.: 31

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.295

Gnomad AMR AF: 0.291

Gnomad ASJ AF: 0.331

Gnomad EAS AF: 0.434

Gnomad SAS AF: 0.249

Gnomad FIN AF: 0.355

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.352

Gnomad OTH AF: 0.313

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

GnomAD4 genome AF: 0.303 AC: 46098 AN: 151970 Hom.: 7505 Cov.: 31 AF XY: 0.303 AC XY: 22502 AN XY: 74264

African (AFR) AF: 0.203 AC: 8405 AN: 41466

American (AMR) AF: 0.291 AC: 4447 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.331 AC: 1146 AN: 3466

East Asian (EAS) AF: 0.435 AC: 2238 AN: 5150

South Asian (SAS) AF: 0.248 AC: 1190 AN: 4806

European-Finnish (FIN) AF: 0.355 AC: 3747 AN: 10542

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.352 AC: 23917 AN: 67958

Other (OTH) AF: 0.314 AC: 660 AN: 2104

Alfa AF: 0.340 Hom.: 37627

Bravo AF: 0.299

Asia WGS AF: 0.303 AC: 1054 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.4
DANN	Benign	0.72
PhyloP100		0.15
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: rs10270663; hg19: chr7-34786398;