rs887020

chr7-34658370-A-Gchr7-34658370-A-T

Variant summary

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

The NM_207172.2(NPSR1):c.-43A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.542 in 1,606,998 control chromosomes in the GnomAD database, including 244,310 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 0.45 (17835 hom., cov: 33)
  • Exomes 𝑓: 0.55 (226475 hom.)
• Consequence: NPSR1 NM_207172.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.20

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 (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.768 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPSR1	NM_207172.2	c.-43A>G		5_prime_UTR_variant	1/9	ENST00000360581.6
NPSR1-AS1	NR_033665.1	n.279+70367T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPSR1	ENST00000360581.6	c.-43A>G		5_prime_UTR_variant	1/9	1	NM_207172.2	P1
NPSR1-AS1	ENST00000419766.5	n.241+70367T>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.447 AC: 68033 AN: 152036 Hom.: 17822 Cov.: 33

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.597

Gnomad AMR AF: 0.497

Gnomad ASJ AF: 0.471

Gnomad EAS AF: 0.788

Gnomad SAS AF: 0.573

Gnomad FIN AF: 0.543

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.554

Gnomad OTH AF: 0.440

GnomAD3 exomes AF: 0.543 AC: 133903 AN: 246668 Hom.: 38375 AF XY: 0.548 AC XY: 72995 AN XY: 133182

Gnomad AFR exome AF: 0.158

Gnomad AMR exome AF: 0.579

Gnomad ASJ exome AF: 0.465

Gnomad EAS exome AF: 0.790

Gnomad SAS exome AF: 0.568

Gnomad FIN exome AF: 0.547

Gnomad NFE exome AF: 0.547

Gnomad OTH exome AF: 0.530

GnomAD4 exome AF: 0.552 AC: 803026 AN: 1454844 Hom.: 226475 Cov.: 33 AF XY: 0.553 AC XY: 399967 AN XY: 723346

Gnomad4 AFR exome AF: 0.147

Gnomad4 AMR exome AF: 0.569

Gnomad4 ASJ exome AF: 0.467

Gnomad4 EAS exome AF: 0.796

Gnomad4 SAS exome AF: 0.566

Gnomad4 FIN exome AF: 0.556

Gnomad4 NFE exome AF: 0.557

Gnomad4 OTH exome AF: 0.534

GnomAD4 genome AF: 0.447 AC: 68072 AN: 152154 Hom.: 17835 Cov.: 33 AF XY: 0.452 AC XY: 33594 AN XY: 74388

Gnomad4 AFR AF: 0.168

Gnomad4 AMR AF: 0.497

Gnomad4 ASJ AF: 0.471

Gnomad4 EAS AF: 0.788

Gnomad4 SAS AF: 0.573

Gnomad4 FIN AF: 0.543

Gnomad4 NFE AF: 0.554

Gnomad4 OTH AF: 0.441

Alfa AF: 0.530 Hom.: 27968

Bravo AF: 0.429

Asia WGS AF: 0.626 AC: 2178 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.087
DANN	Benign	0.47

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: rs887020; hg19: chr7-34697982; COSMIC: COSV62199271; COSMIC: COSV62199271;