7-34834426-C-G

Variant names:

• chr7-34834426-C-G
• rs727162
• NM_207172.2:c.723C>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.723C>G​(p.Ser241Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 1,608,648 control chromosomes in the GnomAD database, including 48,112 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 0.25 (5093 hom., cov: 32)
  • Exomes 𝑓: 0.23 (43019 hom.)
• Consequence: NPSR1 NM_207172.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.24
• Publications: 35 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 (MetaRNN=0.004612893).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPSR1	NM_207172.2	c.723C>G	p.Ser241Arg	missense_variant	Exon 6 of 9	ENST00000360581.6	NP_997055.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPSR1	ENST00000360581.6	c.723C>G	p.Ser241Arg	missense_variant	Exon 6 of 9	1	NM_207172.2	ENSP00000353788.1

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38202 AN: 151994 Hom.: 5080 Cov.: 32

Gnomad AFR AF: 0.270

Gnomad AMI AF: 0.128

Gnomad AMR AF: 0.334

Gnomad ASJ AF: 0.240

Gnomad EAS AF: 0.330

Gnomad SAS AF: 0.397

Gnomad FIN AF: 0.236

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.245

GnomAD2 exomes AF: 0.281 AC: 70436 AN: 250900 AF XY: 0.282

Gnomad AFR exome AF: 0.269

Gnomad AMR exome AF: 0.418

Gnomad ASJ exome AF: 0.225

Gnomad EAS exome AF: 0.322

Gnomad FIN exome AF: 0.226

Gnomad NFE exome AF: 0.218

Gnomad OTH exome AF: 0.266

GnomAD4 exome AF: 0.234 AC: 341227 AN: 1456536 Hom.: 43019 Cov.: 31 AF XY: 0.239 AC XY: 173361 AN XY: 724754

African (AFR) AF: 0.275 AC: 9171 AN: 33364

American (AMR) AF: 0.411 AC: 18337 AN: 44638

Ashkenazi Jewish (ASJ) AF: 0.227 AC: 5910 AN: 26080

East Asian (EAS) AF: 0.319 AC: 12666 AN: 39654

South Asian (SAS) AF: 0.398 AC: 34255 AN: 85964

European-Finnish (FIN) AF: 0.222 AC: 11824 AN: 53374

Middle Eastern (MID) AF: 0.316 AC: 1821 AN: 5758

European-Non Finnish (NFE) AF: 0.210 AC: 232419 AN: 1107498

Other (OTH) AF: 0.246 AC: 14824 AN: 60206

GnomAD4 genome AF: 0.251 AC: 38243 AN: 152112 Hom.: 5093 Cov.: 32 AF XY: 0.259 AC XY: 19232 AN XY: 74340

African (AFR) AF: 0.270 AC: 11186 AN: 41464

American (AMR) AF: 0.334 AC: 5105 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.240 AC: 833 AN: 3470

East Asian (EAS) AF: 0.330 AC: 1708 AN: 5168

South Asian (SAS) AF: 0.397 AC: 1913 AN: 4822

European-Finnish (FIN) AF: 0.236 AC: 2495 AN: 10564

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

European-Non Finnish (NFE) AF: 0.210 AC: 14276 AN: 68018

Other (OTH) AF: 0.248 AC: 524 AN: 2116

Alfa AF: 0.185 Hom.: 977

Bravo AF: 0.259

TwinsUK AF: 0.203 AC: 752

ALSPAC AF: 0.204 AC: 788

ESP6500AA AF: 0.268 AC: 1179

ESP6500EA AF: 0.211 AC: 1812

ExAC AF: 0.278 AC: 33717

Asia WGS AF: 0.370 AC: 1287 AN: 3478

EpiCase AF: 0.216

EpiControl AF: 0.220

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.63
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.40
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T;.;.;.;.
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.86	D;D;D;D;D
MetaRNN	Benign	0.0046	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L;.;L;.;L
PhyloP100		1.2
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-2.7	D;N;D;D;D
REVEL	Benign	0.077
Sift	Benign	0.049	D;T;D;T;D
Sift4G	Benign	0.43	T;T;T;T;T
Polyphen		1.0	D;D;D;D;D
Vest4		0.28
MutPred		0.28		Gain of MoRF binding (P = 0.0451);.;Gain of MoRF binding (P = 0.0451);.;Gain of MoRF binding (P = 0.0451);
MPC		0.17
ClinPred		0.018	T
GERP RS		4.8
Varity_R		0.31
gMVP		0.64
Mutation Taster		=93/7	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: rs727162; hg19: chr7-34874038; COSMIC: COSV62198388; COSMIC: COSV62198388;