NM_207172.2:c.680+343T>C

Variant names:

• chr7-34827945-T-C
• rs1419868
• NM_207172.2:c.680+343T>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.680+343T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.642 in 152,130 control chromosomes in the GnomAD database, including 33,031 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 0.64 (33031 hom., cov: 33)
• Consequence: NPSR1 NM_207172.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.464
• 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.856 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207172.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPSR1	NM_207172.2	MANE Select	c.680+343T>C		intron	N/A	NP_997055.1
	NPSR1	NM_001300935.2		c.680+343T>C		intron	N/A	NP_001287864.1
	NPSR1	NM_207173.2		c.680+343T>C		intron	N/A	NP_997056.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPSR1	ENST00000360581.6	TSL:1 MANE Select	c.680+343T>C		intron	N/A	ENSP00000353788.1
	NPSR1	ENST00000381539.3	TSL:1	c.680+343T>C		intron	N/A	ENSP00000370950.3
	NPSR1	ENST00000359791.5	TSL:1	c.680+343T>C		intron	N/A	ENSP00000352839.1

Frequencies

GnomAD3 genomes AF: 0.642 AC: 97540 AN: 152012 Hom.: 32974 Cov.: 33

Gnomad AFR AF: 0.863

Gnomad AMI AF: 0.410

Gnomad AMR AF: 0.506

Gnomad ASJ AF: 0.541

Gnomad EAS AF: 0.730

Gnomad SAS AF: 0.493

Gnomad FIN AF: 0.624

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.553

Gnomad OTH AF: 0.614

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

GnomAD4 genome AF: 0.642 AC: 97646 AN: 152130 Hom.: 33031 Cov.: 33 AF XY: 0.641 AC XY: 47640 AN XY: 74354

African (AFR) AF: 0.863 AC: 35856 AN: 41534

American (AMR) AF: 0.505 AC: 7726 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.541 AC: 1878 AN: 3472

East Asian (EAS) AF: 0.731 AC: 3779 AN: 5168

South Asian (SAS) AF: 0.492 AC: 2371 AN: 4824

European-Finnish (FIN) AF: 0.624 AC: 6600 AN: 10572

Middle Eastern (MID) AF: 0.578 AC: 170 AN: 294

European-Non Finnish (NFE) AF: 0.553 AC: 37599 AN: 67964

Other (OTH) AF: 0.615 AC: 1295 AN: 2106

Alfa AF: 0.566 Hom.: 41250

Bravo AF: 0.648

Asia WGS AF: 0.602 AC: 2094 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.1
DANN	Benign	0.41
PhyloP100		-0.46
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: rs1419868; hg19: chr7-34867557;