7-34834597-C-G

Variant names:

• chr7-34834597-C-G
• rs17170017
• NM_207172.2:c.757+137C>G

Variant summary

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

The NM_207172.2(NPSR1):​c.757+137C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 669,182 control chromosomes in the GnomAD database, including 23,751 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 (4500 hom., cov: 32)
  • Exomes 𝑓: 0.27 (19251 hom.)
• Consequence: NPSR1 NM_207172.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.315
• 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPSR1	NM_207172.2	c.757+137C>G		intron_variant	Intron 6 of 8	ENST00000360581.6	NP_997055.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPSR1	ENST00000360581.6	c.757+137C>G		intron_variant	Intron 6 of 8	1	NM_207172.2	ENSP00000353788.1

Frequencies

GnomAD3 genomes AF: 0.233 AC: 35373 AN: 151910 Hom.: 4496 Cov.: 32

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.167

Gnomad AMR AF: 0.272

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.433

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.266

Gnomad OTH AF: 0.231

GnomAD4 exome AF: 0.267 AC: 138035 AN: 517154 Hom.: 19251 AF XY: 0.263 AC XY: 72671 AN XY: 275980

African (AFR) AF: 0.140 AC: 2003 AN: 14328

American (AMR) AF: 0.329 AC: 9028 AN: 27412

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 3793 AN: 16014

East Asian (EAS) AF: 0.430 AC: 13663 AN: 31758

South Asian (SAS) AF: 0.224 AC: 11362 AN: 50812

European-Finnish (FIN) AF: 0.248 AC: 9927 AN: 40062

Middle Eastern (MID) AF: 0.215 AC: 796 AN: 3702

European-Non Finnish (NFE) AF: 0.263 AC: 80207 AN: 304408

Other (OTH) AF: 0.253 AC: 7256 AN: 28658

GnomAD4 genome AF: 0.233 AC: 35392 AN: 152028 Hom.: 4500 Cov.: 32 AF XY: 0.231 AC XY: 17205 AN XY: 74324

African (AFR) AF: 0.142 AC: 5911 AN: 41482

American (AMR) AF: 0.272 AC: 4153 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.232 AC: 805 AN: 3464

East Asian (EAS) AF: 0.433 AC: 2225 AN: 5144

South Asian (SAS) AF: 0.202 AC: 971 AN: 4810

European-Finnish (FIN) AF: 0.239 AC: 2527 AN: 10570

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.266 AC: 18101 AN: 67976

Other (OTH) AF: 0.229 AC: 483 AN: 2112

Alfa AF: 0.153 Hom.: 343

Bravo AF: 0.232

Asia WGS AF: 0.295 AC: 1025 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.3
DANN	Benign	0.68
PhyloP100		-0.32
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: rs17170017; hg19: chr7-34874209; COSMIC: COSV107454122; COSMIC: COSV107454122;