rs324987

Variant names:

• chr7-34781816-T-C
• rs324987
• NM_207172.2:c.384+3251T>C

Your query was ambiguous. Multiple possible variants found:

• chr7-34781816-T-C
• chr7-34781816-T-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.384+3251T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.472 in 151,950 control chromosomes in the GnomAD database, including 17,298 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 0.47 (17298 hom., cov: 32)
• Consequence: NPSR1 NM_207172.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.634
• Publications: 7 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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.535 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPSR1	NM_207172.2	c.384+3251T>C		intron_variant	Intron 3 of 8	ENST00000360581.6	NP_997055.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPSR1	ENST00000360581.6	c.384+3251T>C		intron_variant	Intron 3 of 8	1	NM_207172.2	ENSP00000353788.1

Frequencies

GnomAD3 genomes AF: 0.472 AC: 71710 AN: 151834 Hom.: 17290 Cov.: 32

Gnomad AFR AF: 0.541

Gnomad AMI AF: 0.439

Gnomad AMR AF: 0.386

Gnomad ASJ AF: 0.429

Gnomad EAS AF: 0.540

Gnomad SAS AF: 0.337

Gnomad FIN AF: 0.487

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.455

Gnomad OTH AF: 0.461

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

GnomAD4 genome AF: 0.472 AC: 71749 AN: 151950 Hom.: 17298 Cov.: 32 AF XY: 0.470 AC XY: 34865 AN XY: 74246

African (AFR) AF: 0.541 AC: 22401 AN: 41444

American (AMR) AF: 0.385 AC: 5888 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.429 AC: 1487 AN: 3468

East Asian (EAS) AF: 0.541 AC: 2770 AN: 5122

South Asian (SAS) AF: 0.336 AC: 1621 AN: 4818

European-Finnish (FIN) AF: 0.487 AC: 5150 AN: 10566

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.455 AC: 30935 AN: 67938

Other (OTH) AF: 0.460 AC: 969 AN: 2108

Alfa AF: 0.455 Hom.: 34009

Bravo AF: 0.473

Asia WGS AF: 0.426 AC: 1481 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.5
DANN	Benign	0.63
PhyloP100		-0.63
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: rs324987; hg19: chr7-34821428;