7-34827512-G-T

Variant names:

• chr7-34827512-G-T
• rs34705969
• NM_207172.2:c.590G>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_207172.2(NPSR1):​c.590G>T​(p.Cys197Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0256 in 1,614,036 control chromosomes in the GnomAD database, including 631 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. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.019 (37 hom., cov: 31)
  • Exomes 𝑓: 0.026 (594 hom.)
• Consequence: NPSR1 NM_207172.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.01

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=0.011187613).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0188 (2865/152220) while in subpopulation NFE AF= 0.0299 (2034/68018). AF 95% confidence interval is 0.0288. There are 37 homozygotes in gnomad4. There are 1353 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 37 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPSR1	NM_207172.2	c.590G>T	p.Cys197Phe	missense_variant	Exon 5 of 9	ENST00000360581.6	NP_997055.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPSR1	ENST00000360581.6	c.590G>T	p.Cys197Phe	missense_variant	Exon 5 of 9	1	NM_207172.2	ENSP00000353788.1

Frequencies

GnomAD3 genomes AF: 0.0189 AC: 2872 AN: 152102 Hom.: 37 Cov.: 31

Gnomad AFR AF: 0.00582

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0158

Gnomad ASJ AF: 0.0210

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00871

Gnomad FIN AF: 0.0174

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0299

Gnomad OTH AF: 0.0206

GnomAD3 exomes AF: 0.0208 AC: 5233 AN: 251298 Hom.: 87 AF XY: 0.0217 AC XY: 2942 AN XY: 135812

Gnomad AFR exome AF: 0.00461

Gnomad AMR exome AF: 0.0152

Gnomad ASJ exome AF: 0.0214

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0106

Gnomad FIN exome AF: 0.0175

Gnomad NFE exome AF: 0.0312

Gnomad OTH exome AF: 0.0269

GnomAD4 exome AF: 0.0264 AC: 38520 AN: 1461816 Hom.: 594 Cov.: 33 AF XY: 0.0260 AC XY: 18901 AN XY: 727228

Gnomad4 AFR exome AF: 0.00418

Gnomad4 AMR exome AF: 0.0155

Gnomad4 ASJ exome AF: 0.0198

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0113

Gnomad4 FIN exome AF: 0.0178

Gnomad4 NFE exome AF: 0.0304

Gnomad4 OTH exome AF: 0.0220

GnomAD4 genome AF: 0.0188 AC: 2865 AN: 152220 Hom.: 37 Cov.: 31 AF XY: 0.0182 AC XY: 1353 AN XY: 74408

Gnomad4 AFR AF: 0.00580

Gnomad4 AMR AF: 0.0158

Gnomad4 ASJ AF: 0.0210

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00831

Gnomad4 FIN AF: 0.0174

Gnomad4 NFE AF: 0.0299

Gnomad4 OTH AF: 0.0204

Alfa AF: 0.0271 Hom.: 146

Bravo AF: 0.0182

TwinsUK AF: 0.0318 AC: 118

ALSPAC AF: 0.0275 AC: 106

ESP6500AA AF: 0.00749 AC: 33

ESP6500EA AF: 0.0298 AC: 256

ExAC AF: 0.0217 AC: 2634

Asia WGS AF: 0.00606 AC: 21 AN: 3478

EpiCase AF: 0.0314

EpiControl AF: 0.0316

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.11
CADD	Pathogenic	29
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.58	D;.;.;.;.
Eigen	Pathogenic	0.89
Eigen_PC	Pathogenic	0.84
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.88	D;D;D;D;D
MetaRNN	Benign	0.011	T;T;T;T;T
MetaSVM	Uncertain	-0.28	T
MutationAssessor	Pathogenic	3.6	H;.;H;.;H
PrimateAI	Uncertain	0.65	T
PROVEAN	Pathogenic	-10	D;D;D;D;D
REVEL	Uncertain	0.42
Sift	Pathogenic	0.0	D;D;D;D;D
Sift4G	Pathogenic	0.0	D;T;D;D;D
Polyphen		1.0	D;D;D;D;D
Vest4		0.48
MPC		0.23
ClinPred		0.12	T
GERP RS		5.4
Varity_R		0.99
gMVP		0.93

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

Publications

LitVar

Other links and lift over

dbSNP: rs34705969; hg19: chr7-34867124;