7-34658764-A-G

Variant names:

• chr7-34658764-A-G
• rs2530552
• NM_207172.2:c.147+205A>G

Variant summary

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

The NM_207172.2(NPSR1):​c.147+205A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 152,102 control chromosomes in the GnomAD database, including 11,365 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 0.38 (11365 hom., cov: 33)
• Consequence: NPSR1 NM_207172.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.242
• Publications: 10 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.443 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPSR1	NM_207172.2	MANE Select	c.147+205A>G		intron	N/A	NP_997055.1	Q6W5P4-1
	NPSR1	NM_001300935.2		c.147+205A>G		intron	N/A	NP_001287864.1	Q6W5P4-3
	NPSR1	NM_207173.2		c.147+205A>G		intron	N/A	NP_997056.1	Q6W5P4-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPSR1	ENST00000360581.6	TSL:1 MANE Select	c.147+205A>G		intron	N/A	ENSP00000353788.1	Q6W5P4-1
	NPSR1	ENST00000381539.3	TSL:1	c.147+205A>G		intron	N/A	ENSP00000370950.3	Q6W5P4-3
	NPSR1	ENST00000359791.5	TSL:1	c.147+205A>G		intron	N/A	ENSP00000352839.1	Q6W5P4-4

Frequencies

GnomAD3 genomes AF: 0.379 AC: 57623 AN: 151982 Hom.: 11358 Cov.: 33

Gnomad AFR AF: 0.438

Gnomad AMI AF: 0.355

Gnomad AMR AF: 0.414

Gnomad ASJ AF: 0.378

Gnomad EAS AF: 0.127

Gnomad SAS AF: 0.457

Gnomad FIN AF: 0.322

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.358

Gnomad OTH AF: 0.389

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

GnomAD4 genome AF: 0.379 AC: 57672 AN: 152102 Hom.: 11365 Cov.: 33 AF XY: 0.381 AC XY: 28296 AN XY: 74350

African (AFR) AF: 0.437 AC: 18131 AN: 41482

American (AMR) AF: 0.414 AC: 6323 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.378 AC: 1312 AN: 3470

East Asian (EAS) AF: 0.127 AC: 659 AN: 5176

South Asian (SAS) AF: 0.459 AC: 2212 AN: 4818

European-Finnish (FIN) AF: 0.322 AC: 3402 AN: 10574

Middle Eastern (MID) AF: 0.442 AC: 129 AN: 292

European-Non Finnish (NFE) AF: 0.358 AC: 24353 AN: 67982

Other (OTH) AF: 0.392 AC: 828 AN: 2114

Alfa AF: 0.371 Hom.: 17824

Bravo AF: 0.387

Asia WGS AF: 0.312 AC: 1086 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.5
DANN	Benign	0.28
PhyloP100		-0.24
PromoterAI		0.0010	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2530552; hg19: chr7-34698376;