chr7-34709170-G-C

Position:

• chr7-34709170-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_207172.2(NPSR1):​c.280+24486G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.448 in 151,828 control chromosomes in the GnomAD database, including 15,962 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 0.45 (15962 hom., cov: 31)
• Consequence: NPSR1 NM_207172.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.113

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.567 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPSR1	NM_207172.2	c.280+24486G>C		intron_variant		ENST00000360581.6	NP_997055.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NPSR1	ENST00000360581.6	c.280+24486G>C		intron_variant		1	NM_207172.2	ENSP00000353788.1

Frequencies

GnomAD3 genomes AF: 0.448 AC: 67976 AN: 151708 Hom.: 15932 Cov.: 31

Gnomad AFR AF: 0.573

Gnomad AMI AF: 0.352

Gnomad AMR AF: 0.349

Gnomad ASJ AF: 0.320

Gnomad EAS AF: 0.507

Gnomad SAS AF: 0.314

Gnomad FIN AF: 0.481

Gnomad MID AF: 0.379

Gnomad NFE AF: 0.403

Gnomad OTH AF: 0.436

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

GnomAD4 genome AF: 0.448 AC: 68048 AN: 151828 Hom.: 15962 Cov.: 31 AF XY: 0.446 AC XY: 33091 AN XY: 74206

Gnomad4 AFR AF: 0.573

Gnomad4 AMR AF: 0.349

Gnomad4 ASJ AF: 0.320

Gnomad4 EAS AF: 0.507

Gnomad4 SAS AF: 0.313

Gnomad4 FIN AF: 0.481

Gnomad4 NFE AF: 0.403

Gnomad4 OTH AF: 0.435

Alfa AF: 0.325 Hom.: 1005

Bravo AF: 0.448

Asia WGS AF: 0.407 AC: 1416 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.26
DANN	Benign	0.31

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

Publications

LitVar

Other links and lift over

dbSNP: rs323922; hg19: chr7-34748782;