rs6958905

Variant names:

• chr7-34849940-T-C
• rs6958905
• ENST00000381544.6:n.*820T>C

Your query was ambiguous. Multiple possible variants found:

• chr7-34849940-T-C
• chr7-34849940-T-G

Variant summary

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

The ENST00000381544.6(NPSR1):​n.*820T>C variant causes a non coding transcript exon 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 ENST00000381544.6 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.156
• Publications: 7 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=-0.86).
• 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 rank	MANE	Protein	UniProt
NPSR1	NM_207172.2	c.*285T>C		3_prime_UTR_variant	Exon 9 of 9	ENST00000360581.6	NP_997055.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPSR1	ENST00000360581.6	c.*285T>C		3_prime_UTR_variant	Exon 9 of 9	1	NM_207172.2	ENSP00000353788.1

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

African (AFR) AF: 0.614 AC: 13558 AN: 22082

American (AMR) AF: 0.274 AC: 2468 AN: 9016

Ashkenazi Jewish (ASJ) AF: 0.342 AC: 3929 AN: 11486

East Asian (EAS) AF: 0.202 AC: 3394 AN: 16762

South Asian (SAS) AF: 0.141 AC: 5087 AN: 36090

European-Finnish (FIN) AF: 0.272 AC: 3130 AN: 11492

Middle Eastern (MID) AF: 0.355 AC: 893 AN: 2516

European-Non Finnish (NFE) AF: 0.351 AC: 308590 AN: 878398

Other (OTH) AF: 0.338 AC: 13165 AN: 38966

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

African (AFR) AF: 0.602 AC: 24917 AN: 41416

American (AMR) AF: 0.319 AC: 4884 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.353 AC: 1223 AN: 3466

East Asian (EAS) AF: 0.204 AC: 1054 AN: 5170

South Asian (SAS) AF: 0.167 AC: 805 AN: 4824

European-Finnish (FIN) AF: 0.289 AC: 3044 AN: 10548

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

European-Non Finnish (NFE) AF: 0.350 AC: 23789 AN: 67934

Other (OTH) AF: 0.393 AC: 828 AN: 2106

Alfa AF: 0.374 Hom.: 13979

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
PhyloP100		-0.16
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: rs6958905; hg19: chr7-34889552;