rs887020

Variant names:

• chr7-34658370-A-G
• rs887020
• NM_207172.2:c.-43A>G

Your query was ambiguous. Multiple possible variants found:

• chr7-34658370-A-G
• chr7-34658370-A-T

Variant summary

Our verdict is Benign. The variant received -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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
NPSR1	NM_207172.2	c.-43A>G		5_prime_UTR_variant	Exon 1 of 9	ENST00000360581.6	NP_997055.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPSR1	ENST00000360581	c.-43A>G		5_prime_UTR_variant	Exon 1 of 9	1	NM_207172.2	ENSP00000353788.1

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

GnomAD2 exomes AF: 0.543 AC: 133903 AN: 246668 AF XY: 0.548

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 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 AC: 4896 AN: 33354

Gnomad4 AMR exome AF: 0.569 AC: 25264 AN: 44402

Gnomad4 ASJ exome AF: 0.467 AC: 12014 AN: 25744

Gnomad4 EAS exome AF: 0.796 AC: 31568 AN: 39636

Gnomad4 SAS exome AF: 0.566 AC: 48445 AN: 85586

Gnomad4 FIN exome AF: 0.556 AC: 29515 AN: 53120

Gnomad4 NFE exome AF: 0.557 AC: 617418 AN: 1108548

Gnomad4 Remaining exome AF: 0.534 AC: 32052 AN: 60020

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 AC: 0.168223 AN: 0.168223

Gnomad4 AMR AF: 0.497 AC: 0.497254 AN: 0.497254

Gnomad4 ASJ AF: 0.471 AC: 0.471165 AN: 0.471165

Gnomad4 EAS AF: 0.788 AC: 0.788178 AN: 0.788178

Gnomad4 SAS AF: 0.573 AC: 0.573237 AN: 0.573237

Gnomad4 FIN AF: 0.543 AC: 0.542887 AN: 0.542887

Gnomad4 NFE AF: 0.554 AC: 0.554316 AN: 0.554316

Gnomad4 OTH AF: 0.441 AC: 0.440758 AN: 0.440758

Alfa AF: 0.519 Hom.: 33964

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
Mutation Taster		=300/0	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

Publications

LitVar

Other links and lift over

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