7-34690655-T-C

Variant names:

• chr7-34690655-T-C
• rs13246143
• NM_207172.2:c.280+5971T>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.280+5971T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 152,142 control chromosomes in the GnomAD database, including 4,100 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 0.22 (4100 hom., cov: 32)
• Consequence: NPSR1 NM_207172.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.118
• Publications: 3 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=-0.79).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.333 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPSR1	NM_207172.2	c.280+5971T>C		intron_variant	Intron 2 of 8	ENST00000360581.6	NP_997055.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPSR1	ENST00000360581.6	c.280+5971T>C		intron_variant	Intron 2 of 8	1	NM_207172.2	ENSP00000353788.1

Frequencies

GnomAD3 genomes AF: 0.224 AC: 34083 AN: 152024 Hom.: 4095 Cov.: 32

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.0572

Gnomad SAS AF: 0.345

Gnomad FIN AF: 0.213

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.234

Gnomad OTH AF: 0.224

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

GnomAD4 genome AF: 0.224 AC: 34111 AN: 152142 Hom.: 4100 Cov.: 32 AF XY: 0.227 AC XY: 16872 AN XY: 74394

African (AFR) AF: 0.195 AC: 8080 AN: 41522

American (AMR) AF: 0.281 AC: 4304 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 822 AN: 3466

East Asian (EAS) AF: 0.0573 AC: 297 AN: 5180

South Asian (SAS) AF: 0.347 AC: 1674 AN: 4820

European-Finnish (FIN) AF: 0.213 AC: 2253 AN: 10558

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.234 AC: 15923 AN: 67988

Other (OTH) AF: 0.226 AC: 478 AN: 2112

Alfa AF: 0.142 Hom.: 311

Bravo AF: 0.226

Asia WGS AF: 0.221 AC: 769 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.6
DANN	Benign	0.92
PhyloP100		0.12
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: rs13246143; hg19: chr7-34730267;