7-34849940-T-C

Position:

• chr7-34849940-T-C

Variant summary

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

The NM_207172.2(NPSR1):​c.*285T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 1,178,762 control chromosomes in the GnomAD database, including 77,215 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 0.40 (13682 hom., cov: 33)
  • Exomes 𝑓: 0.34 (63533 hom.)
• Consequence: NPSR1 NM_207172.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.156

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.595 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPSR1	NM_207172.2	c.*285T>C		3_prime_UTR_variant	9/9	ENST00000360581.6	NP_997055.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NPSR1	ENST00000360581.6	c.*285T>C		3_prime_UTR_variant	9/9	1	NM_207172.2	ENSP00000353788	P1

Frequencies

GnomAD3 genomes AF: 0.402 AC: 61081 AN: 151836 Hom.: 13669 Cov.: 33

Gnomad AFR AF: 0.602

Gnomad AMI AF: 0.502

Gnomad AMR AF: 0.320

Gnomad ASJ AF: 0.353

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.289

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.350

Gnomad OTH AF: 0.397

GnomAD4 exome AF: 0.345 AC: 354214 AN: 1026808 Hom.: 63533 Cov.: 31 AF XY: 0.340 AC XY: 165004 AN XY: 485756

Gnomad4 AFR exome AF: 0.614

Gnomad4 AMR exome AF: 0.274

Gnomad4 ASJ exome AF: 0.342

Gnomad4 EAS exome AF: 0.202

Gnomad4 SAS exome AF: 0.141

Gnomad4 FIN exome AF: 0.272

Gnomad4 NFE exome AF: 0.351

Gnomad4 OTH exome AF: 0.338

GnomAD4 genome AF: 0.402 AC: 61130 AN: 151954 Hom.: 13682 Cov.: 33 AF XY: 0.392 AC XY: 29125 AN XY: 74274

Gnomad4 AFR AF: 0.602

Gnomad4 AMR AF: 0.319

Gnomad4 ASJ AF: 0.353

Gnomad4 EAS AF: 0.204

Gnomad4 SAS AF: 0.167

Gnomad4 FIN AF: 0.289

Gnomad4 NFE AF: 0.350

Gnomad4 OTH AF: 0.393

Alfa AF: 0.363 Hom.: 9978

Bravo AF: 0.419

Asia WGS AF: 0.203 AC: 707 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.2
DANN	Benign	0.69

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: rs6958905; hg19: chr7-34889552;