7-34865194-G-C

Variant names:

• chr7-34865194-G-C
• rs2040854
• ENST00000359791.5:c.1026-12882G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000359791.5(NPSR1):​c.1026-12882G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 151,642 control chromosomes in the GnomAD database, including 4,553 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 0.23 (4553 hom., cov: 32)
• Consequence: NPSR1 ENST00000359791.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00800
• Publications: 2 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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.454 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPSR1	NM_207173.2	c.1026-12882G>C		intron_variant	Intron 8 of 8		NP_997056.1
NPSR1	NM_001300933.2	c.993-12882G>C		intron_variant	Intron 8 of 8		NP_001287862.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPSR1	ENST00000359791.5	c.1026-12882G>C		intron_variant	Intron 8 of 8	1		ENSP00000352839.1
NPSR1	ENST00000531252.5	c.993-12882G>C		intron_variant	Intron 8 of 8	1		ENSP00000433258.1
NPSR1-AS1	ENST00000431669.5	n.84+6305C>G		intron_variant	Intron 1 of 3	1

Frequencies

GnomAD3 genomes AF: 0.231 AC: 35062 AN: 151524 Hom.: 4542 Cov.: 32

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.293

Gnomad ASJ AF: 0.271

Gnomad EAS AF: 0.296

Gnomad SAS AF: 0.470

Gnomad FIN AF: 0.242

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.215

Gnomad OTH AF: 0.228

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

GnomAD4 genome AF: 0.231 AC: 35105 AN: 151642 Hom.: 4553 Cov.: 32 AF XY: 0.240 AC XY: 17821 AN XY: 74110

African (AFR) AF: 0.196 AC: 8022 AN: 41032

American (AMR) AF: 0.293 AC: 4475 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.271 AC: 941 AN: 3472

East Asian (EAS) AF: 0.296 AC: 1530 AN: 5170

South Asian (SAS) AF: 0.471 AC: 2265 AN: 4814

European-Finnish (FIN) AF: 0.242 AC: 2558 AN: 10582

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.215 AC: 14614 AN: 67984

Other (OTH) AF: 0.234 AC: 493 AN: 2104

Alfa AF: 0.215 Hom.: 482

Bravo AF: 0.225

Asia WGS AF: 0.399 AC: 1384 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.5
DANN	Benign	0.36
PhyloP100		-0.0080
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2040854; hg19: chr7-34904806;