chr7-34830389-G-A

Variant names:

• chr7-34830389-G-A
• rs12111597
• NM_207172.2:c.680+2787G>A

Variant summary

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

The NM_207172.2(NPSR1):​c.680+2787G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 151,772 control chromosomes in the GnomAD database, including 6,892 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 0.29 (6892 hom., cov: 33)
• Consequence: NPSR1 NM_207172.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.226
• Publications: 6 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.378 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPSR1	NM_207172.2	c.680+2787G>A		intron_variant	Intron 5 of 8	ENST00000360581.6	NP_997055.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPSR1	ENST00000360581.6	c.680+2787G>A		intron_variant	Intron 5 of 8	1	NM_207172.2	ENSP00000353788.1

Frequencies

GnomAD3 genomes AF: 0.290 AC: 44055 AN: 151654 Hom.: 6868 Cov.: 33

Gnomad AFR AF: 0.383

Gnomad AMI AF: 0.201

Gnomad AMR AF: 0.359

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.358

Gnomad SAS AF: 0.381

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.293

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

GnomAD4 genome AF: 0.291 AC: 44126 AN: 151772 Hom.: 6892 Cov.: 33 AF XY: 0.296 AC XY: 21937 AN XY: 74186

African (AFR) AF: 0.383 AC: 15833 AN: 41340

American (AMR) AF: 0.359 AC: 5475 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 818 AN: 3470

East Asian (EAS) AF: 0.359 AC: 1852 AN: 5160

South Asian (SAS) AF: 0.382 AC: 1841 AN: 4814

European-Finnish (FIN) AF: 0.257 AC: 2700 AN: 10498

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.217 AC: 14715 AN: 67914

Other (OTH) AF: 0.295 AC: 623 AN: 2114

Alfa AF: 0.250 Hom.: 11650

Bravo AF: 0.300

Asia WGS AF: 0.388 AC: 1346 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.8
DANN	Benign	0.68
PhyloP100		0.23
Mutation Taster		=100/0	polymorphism (auto)

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: rs12111597; hg19: chr7-34870001;