chr7-34847566-G-T

Variant names:

• chr7-34847566-G-T
• rs13246028
• NM_207172.2:c.845-917G>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.845-917G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 151,756 control chromosomes in the GnomAD database, including 8,566 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 0.33 (8566 hom., cov: 32)
• Consequence: NPSR1 NM_207172.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0330
• Publications: 0 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.378 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.845-917G>T		intron	N/A	NP_997055.1
	NPSR1	NM_001300935.2		c.845-917G>T		intron	N/A	NP_001287864.1
	NPSR1	NM_207173.2		c.845-917G>T		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.845-917G>T		intron	N/A	ENSP00000353788.1
	NPSR1	ENST00000381539.3	TSL:1	c.845-917G>T		intron	N/A	ENSP00000370950.3
	NPSR1	ENST00000359791.5	TSL:1	c.845-917G>T		intron	N/A	ENSP00000352839.1

Frequencies

GnomAD3 genomes AF: 0.330 AC: 50099 AN: 151638 Hom.: 8556 Cov.: 32

Gnomad AFR AF: 0.383

Gnomad AMI AF: 0.474

Gnomad AMR AF: 0.255

Gnomad ASJ AF: 0.338

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.344

Gnomad OTH AF: 0.336

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

GnomAD4 genome AF: 0.330 AC: 50136 AN: 151756 Hom.: 8566 Cov.: 32 AF XY: 0.322 AC XY: 23862 AN XY: 74166

African (AFR) AF: 0.383 AC: 15836 AN: 41338

American (AMR) AF: 0.255 AC: 3889 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.338 AC: 1172 AN: 3464

East Asian (EAS) AF: 0.162 AC: 837 AN: 5164

South Asian (SAS) AF: 0.162 AC: 781 AN: 4816

European-Finnish (FIN) AF: 0.286 AC: 3015 AN: 10536

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.344 AC: 23355 AN: 67858

Other (OTH) AF: 0.331 AC: 697 AN: 2108

Alfa AF: 0.331 Hom.: 10334

Bravo AF: 0.333

Asia WGS AF: 0.158 AC: 549 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.2
DANN	Benign	0.60
PhyloP100		0.033
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: rs13246028; hg19: chr7-34887178;