NM_207172.2:c.147+3628T>C

Variant names:

• chr7-34662187-T-C
• rs425990
• NM_207172.2:c.147+3628T>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.147+3628T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.559 in 151,978 control chromosomes in the GnomAD database, including 25,265 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 0.56 (25265 hom., cov: 32)
• Consequence: NPSR1 NM_207172.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.459

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.758 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPSR1	NM_207172.2	c.147+3628T>C		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.147+3628T>C		intron_variant	Intron 1 of 8	1	NM_207172.2	ENSP00000353788.1

Frequencies

GnomAD3 genomes AF: 0.559 AC: 84866 AN: 151860 Hom.: 25229 Cov.: 32

Gnomad AFR AF: 0.766

Gnomad AMI AF: 0.479

Gnomad AMR AF: 0.515

Gnomad ASJ AF: 0.533

Gnomad EAS AF: 0.242

Gnomad SAS AF: 0.557

Gnomad FIN AF: 0.476

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.482

Gnomad OTH AF: 0.562

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

GnomAD4 genome AF: 0.559 AC: 84957 AN: 151978 Hom.: 25265 Cov.: 32 AF XY: 0.557 AC XY: 41367 AN XY: 74264

African (AFR) AF: 0.765 AC: 31736 AN: 41458

American (AMR) AF: 0.514 AC: 7856 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.533 AC: 1849 AN: 3470

East Asian (EAS) AF: 0.242 AC: 1247 AN: 5160

South Asian (SAS) AF: 0.559 AC: 2694 AN: 4820

European-Finnish (FIN) AF: 0.476 AC: 5021 AN: 10540

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.482 AC: 32763 AN: 67952

Other (OTH) AF: 0.563 AC: 1185 AN: 2106

Alfa AF: 0.545 Hom.: 15238

Bravo AF: 0.571

Asia WGS AF: 0.440 AC: 1529 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.6
DANN	Benign	0.27
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

Publications

LitVar

Other links and lift over

dbSNP: rs425990; hg19: chr7-34701799;