rs324396

Variant names:

• chr7-34750511-T-C
• rs324396
• NM_207172.2:c.281-27951T>C

Your query was ambiguous. Multiple possible variants found:

• chr7-34750511-T-C
• chr7-34750511-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.281-27951T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.686 in 701,190 control chromosomes in the GnomAD database, including 168,283 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 0.74 (42977 hom., cov: 31)
  • Exomes 𝑓: 0.67 (125306 hom.)
• Consequence: NPSR1 NM_207172.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.329
• Publications: 17 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]

NCAPD2P1 (HGNC:43831): (non-SMC condensin I complex subunit D2 pseudogene 1)

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 (AFR) allele frequency at 95% confidence interval = 0.923 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPSR1	NM_207172.2	c.281-27951T>C		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.281-27951T>C		intron_variant	Intron 2 of 8	1	NM_207172.2	ENSP00000353788.1

Frequencies

GnomAD3 genomes AF: 0.741 AC: 112634 AN: 151984 Hom.: 42916 Cov.: 31

Gnomad AFR AF: 0.931

Gnomad AMI AF: 0.649

Gnomad AMR AF: 0.673

Gnomad ASJ AF: 0.653

Gnomad EAS AF: 0.572

Gnomad SAS AF: 0.673

Gnomad FIN AF: 0.665

Gnomad MID AF: 0.683

Gnomad NFE AF: 0.677

Gnomad OTH AF: 0.729

GnomAD4 exome AF: 0.670 AC: 368005 AN: 549088 Hom.: 125306 Cov.: 0 AF XY: 0.670 AC XY: 201328 AN XY: 300568

African (AFR) AF: 0.934 AC: 14436 AN: 15448

American (AMR) AF: 0.627 AC: 23588 AN: 37608

Ashkenazi Jewish (ASJ) AF: 0.653 AC: 10987 AN: 16830

East Asian (EAS) AF: 0.545 AC: 17479 AN: 32054

South Asian (SAS) AF: 0.674 AC: 42472 AN: 62996

European-Finnish (FIN) AF: 0.650 AC: 29573 AN: 45502

Middle Eastern (MID) AF: 0.718 AC: 2550 AN: 3554

European-Non Finnish (NFE) AF: 0.676 AC: 207483 AN: 306772

Other (OTH) AF: 0.686 AC: 19437 AN: 28324

GnomAD4 genome AF: 0.741 AC: 112757 AN: 152102 Hom.: 42977 Cov.: 31 AF XY: 0.738 AC XY: 54883 AN XY: 74324

African (AFR) AF: 0.931 AC: 38656 AN: 41512

American (AMR) AF: 0.673 AC: 10282 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.653 AC: 2267 AN: 3472

East Asian (EAS) AF: 0.572 AC: 2952 AN: 5160

South Asian (SAS) AF: 0.673 AC: 3243 AN: 4816

European-Finnish (FIN) AF: 0.665 AC: 7032 AN: 10572

Middle Eastern (MID) AF: 0.693 AC: 201 AN: 290

European-Non Finnish (NFE) AF: 0.677 AC: 46000 AN: 67980

Other (OTH) AF: 0.727 AC: 1532 AN: 2108

Alfa AF: 0.691 Hom.: 69404

Bravo AF: 0.753

Asia WGS AF: 0.636 AC: 2213 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.2
DANN	Benign	0.73
PhyloP100		0.33
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: rs324396; hg19: chr7-34790123;