rs6972158

Positions:

• chr7-34849570-A-G
• chr7-34849570-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000360581.6(NPSR1):​c.1031A>G​(p.Gln344Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 1,612,262 control chromosomes in the GnomAD database, including 90,615 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/16 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.33 (8702 hom., cov: 33)
  • Exomes 𝑓: 0.33 (81913 hom.)
• Consequence: NPSR1 ENST00000360581.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0880

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005805552).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPSR1	NM_207172.2	c.1031A>G	p.Gln344Arg	missense_variant	9/9	ENST00000360581.6	NP_997055.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NPSR1	ENST00000360581.6	c.1031A>G	p.Gln344Arg	missense_variant	9/9	1	NM_207172.2	ENSP00000353788	P1

Frequencies

GnomAD3 genomes AF: 0.332 AC: 50397 AN: 152022 Hom.: 8692 Cov.: 33

Gnomad AFR AF: 0.384

Gnomad AMI AF: 0.475

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.338

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.345

Gnomad OTH AF: 0.336

GnomAD3 exomes AF: 0.283 AC: 71077 AN: 251364 Hom.: 10901 AF XY: 0.279 AC XY: 37970 AN XY: 135856

Gnomad AFR exome AF: 0.386

Gnomad AMR exome AF: 0.180

Gnomad ASJ exome AF: 0.341

Gnomad EAS exome AF: 0.150

Gnomad SAS exome AF: 0.156

Gnomad FIN exome AF: 0.292

Gnomad NFE exome AF: 0.347

Gnomad OTH exome AF: 0.312

GnomAD4 exome AF: 0.329 AC: 479727 AN: 1460122 Hom.: 81913 Cov.: 35 AF XY: 0.323 AC XY: 234378 AN XY: 726468

Gnomad4 AFR exome AF: 0.390

Gnomad4 AMR exome AF: 0.190

Gnomad4 ASJ exome AF: 0.344

Gnomad4 EAS exome AF: 0.190

Gnomad4 SAS exome AF: 0.161

Gnomad4 FIN exome AF: 0.296

Gnomad4 NFE exome AF: 0.351

Gnomad4 OTH exome AF: 0.325

GnomAD4 genome AF: 0.331 AC: 50434 AN: 152140 Hom.: 8702 Cov.: 33 AF XY: 0.323 AC XY: 24016 AN XY: 74386

Gnomad4 AFR AF: 0.384

Gnomad4 AMR AF: 0.255

Gnomad4 ASJ AF: 0.338

Gnomad4 EAS AF: 0.163

Gnomad4 SAS AF: 0.162

Gnomad4 FIN AF: 0.288

Gnomad4 NFE AF: 0.345

Gnomad4 OTH AF: 0.331

Alfa AF: 0.340 Hom.: 18655

Bravo AF: 0.333

TwinsUK AF: 0.361 AC: 1340

ALSPAC AF: 0.365 AC: 1406

ESP6500AA AF: 0.392 AC: 1728

ESP6500EA AF: 0.349 AC: 3005

ExAC AF: 0.287 AC: 34796

Asia WGS AF: 0.158 AC: 548 AN: 3478

EpiCase AF: 0.351

EpiControl AF: 0.343

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.056
BayesDel_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.21
DANN	Benign	0.61
DEOGEN2	Benign	0.048	T;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0084	N
LIST_S2	Benign	0.28	T;T
MetaRNN	Benign	0.0058	T;T
MetaSVM	Benign	-0.91	T
MutationTaster	Benign	1.0	P;P;P;P;P
PROVEAN	Benign	0.45	N;N
REVEL	Benign	0.025
Sift	Benign	0.87	T;T
Sift4G	Benign	0.95	T;T
Polyphen		0.0	B;B
Vest4		0.066
ClinPred		0.0067	T
GERP RS		-1.2
Varity_R		0.037

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs6972158; hg19: chr7-34889182; COSMIC: COSV62198297;