rs324396

Positions:

• chr7-34750511-T-C
• chr7-34750511-T-G

Variant summary

Our verdict is Benign. Variant got -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

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]

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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
NPSR1	NM_207172.2	c.281-27951T>C		intron_variant		ENST00000360581.6
NPSR1-AS1	NR_033665.1	n.199+7563A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPSR1	ENST00000360581.6	c.281-27951T>C		intron_variant		1	NM_207172.2	P1
NCAPD2P1	ENST00000432906.1	n.1543A>G		non_coding_transcript_exon_variant	1/1
NPSR1-AS1	ENST00000419766.5	n.161+7563A>G		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR exome AF: 0.934

Gnomad4 AMR exome AF: 0.627

Gnomad4 ASJ exome AF: 0.653

Gnomad4 EAS exome AF: 0.545

Gnomad4 SAS exome AF: 0.674

Gnomad4 FIN exome AF: 0.650

Gnomad4 NFE exome AF: 0.676

Gnomad4 OTH exome AF: 0.686

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

Gnomad4 AFR AF: 0.931

Gnomad4 AMR AF: 0.673

Gnomad4 ASJ AF: 0.653

Gnomad4 EAS AF: 0.572

Gnomad4 SAS AF: 0.673

Gnomad4 FIN AF: 0.665

Gnomad4 NFE AF: 0.677

Gnomad4 OTH AF: 0.727

Alfa AF: 0.689 Hom.: 47115

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

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: rs324396; hg19: chr7-34790123;