7-34658019-G-C

Variant names:

• chr7-34658019-G-C
• rs1419793
• ENST00000358772.8:n.279+70718C>G

Variant summary

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

The ENST00000358772.8(NPSR1-AS1):​n.279+70718C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0492 in 152,242 control chromosomes in the GnomAD database, including 349 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 0.049 (349 hom., cov: 33)
• Consequence: NPSR1-AS1 ENST00000358772.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0880
• Publications: 4 publications found

Genes affected

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]

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.125 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPSR1	NM_207172.2	c.-394G>C		upstream_gene_variant		ENST00000360581.6	NP_997055.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPSR1	ENST00000360581.6	c.-394G>C		upstream_gene_variant		1	NM_207172.2	ENSP00000353788.1

Frequencies

GnomAD3 genomes AF: 0.0492 AC: 7485 AN: 152124 Hom.: 350 Cov.: 33

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0319

Gnomad ASJ AF: 0.0225

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00829

Gnomad FIN AF: 0.00320

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0209

Gnomad OTH AF: 0.0416

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

GnomAD4 genome AF: 0.0492 AC: 7494 AN: 152242 Hom.: 349 Cov.: 33 AF XY: 0.0471 AC XY: 3506 AN XY: 74454

African (AFR) AF: 0.128 AC: 5325 AN: 41512

American (AMR) AF: 0.0319 AC: 487 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0225 AC: 78 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00850 AC: 41 AN: 4824

European-Finnish (FIN) AF: 0.00320 AC: 34 AN: 10618

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0209 AC: 1419 AN: 68022

Other (OTH) AF: 0.0412 AC: 87 AN: 2114

Alfa AF: 0.0383 Hom.: 40

Bravo AF: 0.0566

Asia WGS AF: 0.0110 AC: 40 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	3.2
DANN	Benign	0.70
PhyloP100		-0.088
PromoterAI		0.0089	Neutral

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: rs1419793; hg19: chr7-34697631;