chr7-34658370-A-G

Variant names:

• chr7-34658370-A-G
• rs887020
• ENST00000381544.6:n.-43A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000381544.6(NPSR1):​n.-43A>G variant causes a non coding transcript exon 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 ENST00000381544.6 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.20
• Publications: 17 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 (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	ENST00000360581.6	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

African (AFR) AF: 0.147 AC: 4896 AN: 33354

American (AMR) AF: 0.569 AC: 25264 AN: 44402

Ashkenazi Jewish (ASJ) AF: 0.467 AC: 12014 AN: 25744

East Asian (EAS) AF: 0.796 AC: 31568 AN: 39636

South Asian (SAS) AF: 0.566 AC: 48445 AN: 85586

European-Finnish (FIN) AF: 0.556 AC: 29515 AN: 53120

Middle Eastern (MID) AF: 0.418 AC: 1854 AN: 4434

European-Non Finnish (NFE) AF: 0.557 AC: 617418 AN: 1108548

Other (OTH) 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

African (AFR) AF: 0.168 AC: 6988 AN: 41540

American (AMR) AF: 0.497 AC: 7606 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.471 AC: 1634 AN: 3468

East Asian (EAS) AF: 0.788 AC: 4067 AN: 5160

South Asian (SAS) AF: 0.573 AC: 2763 AN: 4820

European-Finnish (FIN) AF: 0.543 AC: 5747 AN: 10586

Middle Eastern (MID) AF: 0.398 AC: 117 AN: 294

European-Non Finnish (NFE) AF: 0.554 AC: 37678 AN: 67972

Other (OTH) AF: 0.441 AC: 930 AN: 2110

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
PhyloP100		-4.2
PromoterAI		0.00070	Neutral
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

Other links and lift over

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