chr7-34728499-G-A

Variant names:

• chr7-34728499-G-A
• rs324381
• NM_207172.2:c.280+43815G>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.280+43815G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 152,110 control chromosomes in the GnomAD database, including 7,688 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 0.31 (7688 hom., cov: 32)
• Consequence: NPSR1 NM_207172.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.891
• Publications: 1 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.423 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPSR1	NM_207172.2	c.280+43815G>A		intron_variant	Intron 2 of 8	ENST00000360581.6	NP_997055.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPSR1	ENST00000360581.6	c.280+43815G>A		intron_variant	Intron 2 of 8	1	NM_207172.2	ENSP00000353788.1

Frequencies

GnomAD3 genomes AF: 0.310 AC: 47179 AN: 151990 Hom.: 7685 Cov.: 32

Gnomad AFR AF: 0.238

Gnomad AMI AF: 0.295

Gnomad AMR AF: 0.291

Gnomad ASJ AF: 0.324

Gnomad EAS AF: 0.437

Gnomad SAS AF: 0.251

Gnomad FIN AF: 0.355

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.346

Gnomad OTH AF: 0.316

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

GnomAD4 genome AF: 0.310 AC: 47214 AN: 152110 Hom.: 7688 Cov.: 32 AF XY: 0.310 AC XY: 23057 AN XY: 74362

African (AFR) AF: 0.238 AC: 9890 AN: 41480

American (AMR) AF: 0.291 AC: 4452 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.324 AC: 1123 AN: 3470

East Asian (EAS) AF: 0.438 AC: 2266 AN: 5172

South Asian (SAS) AF: 0.250 AC: 1204 AN: 4822

European-Finnish (FIN) AF: 0.355 AC: 3756 AN: 10578

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

European-Non Finnish (NFE) AF: 0.346 AC: 23506 AN: 67982

Other (OTH) AF: 0.317 AC: 669 AN: 2108

Alfa AF: 0.331 Hom.: 1941

Bravo AF: 0.306

Asia WGS AF: 0.306 AC: 1065 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.18
DANN	Benign	0.46
PhyloP100		-0.89
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: rs324381; hg19: chr7-34768111;