chr7-34878090-G-A

Variant names:

• chr7-34878090-G-A
• rs28480169
• ENST00000359791.5:c.1040G>A

Variant summary

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

The ENST00000359791.5(NPSR1):​c.1040G>A​(p.Arg347His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0738 in 1,598,622 control chromosomes in the GnomAD database, including 5,124 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.065 (453 hom., cov: 32)
  • Exomes 𝑓: 0.075 (4671 hom.)
• Consequence: NPSR1 ENST00000359791.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.112
• Publications: 10 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.0017320514).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0829 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000359791.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPSR1	NM_207173.2		c.1040G>A	p.Arg347His	missense	Exon 9 of 9	NP_997056.1
	NPSR1	NM_001300933.2		c.1007G>A	p.Arg336His	missense	Exon 9 of 9	NP_001287862.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPSR1	ENST00000359791.5	TSL:1	c.1040G>A	p.Arg347His	missense	Exon 9 of 9	ENSP00000352839.1
	NPSR1	ENST00000531252.5	TSL:1	c.1007G>A	p.Arg336His	missense	Exon 9 of 9	ENSP00000433258.1

Frequencies

GnomAD3 genomes AF: 0.0651 AC: 9904 AN: 152084 Hom.: 453 Cov.: 32

Gnomad AFR AF: 0.0237

Gnomad AMI AF: 0.205

Gnomad AMR AF: 0.0609

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.0122

Gnomad SAS AF: 0.0570

Gnomad FIN AF: 0.0841

Gnomad MID AF: 0.162

Gnomad NFE AF: 0.0848

Gnomad OTH AF: 0.0870

GnomAD2 exomes AF: 0.0670 AC: 16185 AN: 241456 AF XY: 0.0697

Gnomad AFR exome AF: 0.0208

Gnomad AMR exome AF: 0.0449

Gnomad ASJ exome AF: 0.162

Gnomad EAS exome AF: 0.00189

Gnomad FIN exome AF: 0.0825

Gnomad NFE exome AF: 0.0821

Gnomad OTH exome AF: 0.0815

GnomAD4 exome AF: 0.0748 AC: 108127 AN: 1446420 Hom.: 4671 Cov.: 29 AF XY: 0.0755 AC XY: 54332 AN XY: 719284

African (AFR) AF: 0.0215 AC: 714 AN: 33240

American (AMR) AF: 0.0478 AC: 2118 AN: 44310

Ashkenazi Jewish (ASJ) AF: 0.163 AC: 4219 AN: 25844

East Asian (EAS) AF: 0.0249 AC: 982 AN: 39428

South Asian (SAS) AF: 0.0579 AC: 4909 AN: 84826

European-Finnish (FIN) AF: 0.0849 AC: 4506 AN: 53046

Middle Eastern (MID) AF: 0.131 AC: 746 AN: 5712

European-Non Finnish (NFE) AF: 0.0775 AC: 85229 AN: 1100186

Other (OTH) AF: 0.0786 AC: 4704 AN: 59828

GnomAD4 genome AF: 0.0650 AC: 9900 AN: 152202 Hom.: 453 Cov.: 32 AF XY: 0.0647 AC XY: 4812 AN XY: 74404

African (AFR) AF: 0.0237 AC: 983 AN: 41550

American (AMR) AF: 0.0608 AC: 929 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 575 AN: 3468

East Asian (EAS) AF: 0.0122 AC: 63 AN: 5154

South Asian (SAS) AF: 0.0575 AC: 277 AN: 4818

European-Finnish (FIN) AF: 0.0841 AC: 890 AN: 10584

Middle Eastern (MID) AF: 0.168 AC: 49 AN: 292

European-Non Finnish (NFE) AF: 0.0848 AC: 5766 AN: 68018

Other (OTH) AF: 0.0856 AC: 181 AN: 2114

Alfa AF: 0.0789 Hom.: 1775

Bravo AF: 0.0607

TwinsUK AF: 0.0868 AC: 322

ALSPAC AF: 0.0714 AC: 275

ESP6500AA AF: 0.0252 AC: 111

ESP6500EA AF: 0.0872 AC: 750

ExAC AF: 0.0652 AC: 7917

Asia WGS AF: 0.0300 AC: 105 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	7.9
DANN	Benign	0.84
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0054	N
LIST_S2	Benign	0.44	T
MetaRNN	Benign	0.0017	T
MetaSVM	Benign	-1.1	T
PhyloP100		0.11
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-0.82	N
REVEL	Benign	0.066
Sift	Uncertain	0.021	D
Sift4G	Uncertain	0.060	T
Polyphen		0.0	B
Vest4		0.0050
MPC		0.028
ClinPred		0.0016	T
GERP RS		0.48
Mutation Taster		=99/1	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs28480169; hg19: chr7-34917702; COSMIC: COSV63106694;