7-34868174-A-T

Variant names:

• chr7-34868174-A-T
• rs1833090
• ENST00000359791.5:c.1026-9902A>T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_207173.2(NPSR1):​c.1026-9902A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00376 in 151,450 control chromosomes in the GnomAD database, including 15 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 0.0038 (15 hom., cov: 30)
• Consequence: NPSR1 NM_207173.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.87

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BS2: High Homozygotes in GnomAd4 at 15 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPSR1	NM_207173.2	c.1026-9902A>T		intron_variant	Intron 8 of 8		NP_997056.1
NPSR1	NM_001300933.2	c.993-9902A>T		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.1026-9902A>T		intron_variant	Intron 8 of 8	1		ENSP00000352839.1
NPSR1	ENST00000531252.5	c.993-9902A>T		intron_variant	Intron 8 of 8	1		ENSP00000433258.1
NPSR1-AS1	ENST00000431669.5	n.84+3325T>A		intron_variant	Intron 1 of 3	1

Frequencies

GnomAD3 genomes AF: 0.00375 AC: 568 AN: 151330 Hom.: 15 Cov.: 30

Gnomad AFR AF: 0.0121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00374

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00528

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

GnomAD4 genome AF: 0.00376 AC: 570 AN: 151450 Hom.: 15 Cov.: 30 AF XY: 0.00354 AC XY: 262 AN XY: 74024

Gnomad4 AFR AF: 0.0121

Gnomad4 AMR AF: 0.00373

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000883

Gnomad4 OTH AF: 0.00523

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.17
DANN	Benign	0.18

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1833090; hg19: chr7-34907786;