rs324966

Positions:

• chr7-34755802-G-A
• chr7-34755802-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_207172.2(NPSR1):​c.281-22660G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 151,514 control chromosomes in the GnomAD database, including 8,259 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 0.33 (8259 hom., cov: 31)
• Consequence: NPSR1 NM_207172.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.546

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

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 = 0.379 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPSR1	NM_207172.2	c.281-22660G>A		intron_variant		ENST00000360581.6	NP_997055.1
NPSR1-AS1	NR_033665.1	n.199+2272C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NPSR1	ENST00000360581.6	c.281-22660G>A		intron_variant		1	NM_207172.2	ENSP00000353788	P1
NPSR1-AS1	ENST00000419766.5	n.161+2272C>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.329 AC: 49761 AN: 151396 Hom.: 8257 Cov.: 31

Gnomad AFR AF: 0.385

Gnomad AMI AF: 0.353

Gnomad AMR AF: 0.274

Gnomad ASJ AF: 0.326

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.249

Gnomad FIN AF: 0.296

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.325

Gnomad OTH AF: 0.333

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

GnomAD4 genome AF: 0.329 AC: 49774 AN: 151514 Hom.: 8259 Cov.: 31 AF XY: 0.324 AC XY: 23946 AN XY: 73960

Gnomad4 AFR AF: 0.384

Gnomad4 AMR AF: 0.273

Gnomad4 ASJ AF: 0.326

Gnomad4 EAS AF: 0.222

Gnomad4 SAS AF: 0.249

Gnomad4 FIN AF: 0.296

Gnomad4 NFE AF: 0.326

Gnomad4 OTH AF: 0.331

Alfa AF: 0.147 Hom.: 229

Bravo AF: 0.332

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.9
DANN	Benign	0.62

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: rs324966; hg19: chr7-34795414;