7-34702031-C-G

Variant names:

• chr7-34702031-C-G
• rs323917
• NM_207172.2:c.280+17347C>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.280+17347C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0683 in 152,228 control chromosomes in the GnomAD database, including 397 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 0.068 (397 hom., cov: 33)
• Consequence: NPSR1 NM_207172.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.765
• Publications: 8 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 (SAS) allele frequency at 95% confidence interval = 0.0822 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPSR1	NM_207172.2	c.280+17347C>G		intron_variant	Intron 2 of 8	ENST00000360581.6	NP_997055.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPSR1	ENST00000360581.6	c.280+17347C>G		intron_variant	Intron 2 of 8	1	NM_207172.2	ENSP00000353788.1

Frequencies

GnomAD3 genomes AF: 0.0683 AC: 10389 AN: 152110 Hom.: 399 Cov.: 33

Gnomad AFR AF: 0.0841

Gnomad AMI AF: 0.0614

Gnomad AMR AF: 0.0650

Gnomad ASJ AF: 0.0674

Gnomad EAS AF: 0.0514

Gnomad SAS AF: 0.0886

Gnomad FIN AF: 0.0637

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0600

Gnomad OTH AF: 0.0755

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

GnomAD4 genome AF: 0.0683 AC: 10403 AN: 152228 Hom.: 397 Cov.: 33 AF XY: 0.0687 AC XY: 5116 AN XY: 74416

African (AFR) AF: 0.0841 AC: 3493 AN: 41528

American (AMR) AF: 0.0649 AC: 993 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0674 AC: 234 AN: 3470

East Asian (EAS) AF: 0.0513 AC: 266 AN: 5184

South Asian (SAS) AF: 0.0891 AC: 430 AN: 4824

European-Finnish (FIN) AF: 0.0637 AC: 674 AN: 10586

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0600 AC: 4084 AN: 68012

Other (OTH) AF: 0.0766 AC: 162 AN: 2114

Alfa AF: 0.0225 Hom.: 17

Bravo AF: 0.0684

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.77
DANN	Benign	0.75
PhyloP100		-0.77
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: rs323917; hg19: chr7-34741643;