rs432478

chr7-34670291-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.147+11732T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 151,632 control chromosomes in the GnomAD database, including 8,166 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 0.30 (8166 hom., cov: 32)
• Consequence: NPSR1 NM_207172.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19

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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.513 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPSR1	NM_207172.2	c.147+11732T>G		intron_variant		ENST00000360581.6
NPSR1-AS1	NR_033665.1	n.279+58446A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPSR1	ENST00000360581.6	c.147+11732T>G		intron_variant		1	NM_207172.2	P1
NPSR1-AS1	ENST00000419766.5	n.241+58446A>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45274 AN: 151510 Hom.: 8153 Cov.: 32

Gnomad AFR AF: 0.519

Gnomad AMI AF: 0.246

Gnomad AMR AF: 0.199

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.179

Gnomad SAS AF: 0.208

Gnomad FIN AF: 0.242

Gnomad MID AF: 0.255

Gnomad NFE AF: 0.214

Gnomad OTH AF: 0.299

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

GnomAD4 genome AF: 0.299 AC: 45339 AN: 151632 Hom.: 8166 Cov.: 32 AF XY: 0.296 AC XY: 21926 AN XY: 74116

Gnomad4 AFR AF: 0.519

Gnomad4 AMR AF: 0.199

Gnomad4 ASJ AF: 0.267

Gnomad4 EAS AF: 0.179

Gnomad4 SAS AF: 0.209

Gnomad4 FIN AF: 0.242

Gnomad4 NFE AF: 0.214

Gnomad4 OTH AF: 0.298

Alfa AF: 0.265 Hom.: 801

Bravo AF: 0.308

Asia WGS AF: 0.208 AC: 715 AN: 3454

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	1.5
Dann	Benign	0.65

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: rs432478; hg19: chr7-34709903;