NM_207172.2:c.148-12395G>A

Variant names:

• chr7-34672157-G-A
• rs963218
• NM_207172.2:c.148-12395G>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.148-12395G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.533 in 152,080 control chromosomes in the GnomAD database, including 23,224 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 0.53 (23224 hom., cov: 33)
• Consequence: NPSR1 NM_207172.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.464
• Publications: 5 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.743 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPSR1	NM_207172.2	c.148-12395G>A		intron_variant	Intron 1 of 8	ENST00000360581.6	NP_997055.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPSR1	ENST00000360581.6	c.148-12395G>A		intron_variant	Intron 1 of 8	1	NM_207172.2	ENSP00000353788.1

Frequencies

GnomAD3 genomes AF: 0.533 AC: 80999 AN: 151962 Hom.: 23190 Cov.: 33

Gnomad AFR AF: 0.750

Gnomad AMI AF: 0.460

Gnomad AMR AF: 0.493

Gnomad ASJ AF: 0.449

Gnomad EAS AF: 0.236

Gnomad SAS AF: 0.538

Gnomad FIN AF: 0.465

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.448

Gnomad OTH AF: 0.532

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

GnomAD4 genome AF: 0.533 AC: 81087 AN: 152080 Hom.: 23224 Cov.: 33 AF XY: 0.534 AC XY: 39665 AN XY: 74338

African (AFR) AF: 0.750 AC: 31130 AN: 41510

American (AMR) AF: 0.492 AC: 7525 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.449 AC: 1557 AN: 3466

East Asian (EAS) AF: 0.236 AC: 1222 AN: 5172

South Asian (SAS) AF: 0.541 AC: 2608 AN: 4824

European-Finnish (FIN) AF: 0.465 AC: 4897 AN: 10522

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.448 AC: 30448 AN: 67982

Other (OTH) AF: 0.534 AC: 1130 AN: 2116

Alfa AF: 0.511 Hom.: 3278

Bravo AF: 0.545

Asia WGS AF: 0.429 AC: 1491 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.7
DANN	Benign	0.63
PhyloP100		0.46
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: rs963218; hg19: chr7-34711769;