7-34679937-T-C

Variant names:

• chr7-34679937-T-C
• rs2531841
• NM_207172.2:c.148-4615T>C

Variant summary

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

The NM_207172.2(NPSR1):​c.148-4615T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.546 in 151,806 control chromosomes in the GnomAD database, including 24,185 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 0.55 (24185 hom., cov: 32)
• Consequence: NPSR1 NM_207172.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27
• Publications: 5 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.751 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPSR1	NM_207172.2	c.148-4615T>C		intron_variant	Intron 1 of 8	ENST00000360581.6	NP_997055.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPSR1	ENST00000360581.6	c.148-4615T>C		intron_variant	Intron 1 of 8	1	NM_207172.2	ENSP00000353788.1

Frequencies

GnomAD3 genomes AF: 0.546 AC: 82755 AN: 151686 Hom.: 24148 Cov.: 32

Gnomad AFR AF: 0.759

Gnomad AMI AF: 0.478

Gnomad AMR AF: 0.502

Gnomad ASJ AF: 0.518

Gnomad EAS AF: 0.235

Gnomad SAS AF: 0.542

Gnomad FIN AF: 0.461

Gnomad MID AF: 0.533

Gnomad NFE AF: 0.465

Gnomad OTH AF: 0.547

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.546 AC: 82848 AN: 151806 Hom.: 24185 Cov.: 32 AF XY: 0.544 AC XY: 40352 AN XY: 74184

African (AFR) AF: 0.758 AC: 31435 AN: 41458

American (AMR) AF: 0.502 AC: 7649 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.518 AC: 1794 AN: 3464

East Asian (EAS) AF: 0.235 AC: 1212 AN: 5164

South Asian (SAS) AF: 0.545 AC: 2626 AN: 4822

European-Finnish (FIN) AF: 0.461 AC: 4839 AN: 10494

Middle Eastern (MID) AF: 0.549 AC: 156 AN: 284

European-Non Finnish (NFE) AF: 0.465 AC: 31548 AN: 67860

Other (OTH) AF: 0.548 AC: 1154 AN: 2106

Alfa AF: 0.497 Hom.: 39500

Bravo AF: 0.559

Asia WGS AF: 0.429 AC: 1473 AN: 3442

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.41
DANN	Benign	0.90
PhyloP100		-1.3
Mutation Taster		=100/0	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: rs2531841; hg19: chr7-34719549;