7-34878090-G-T

Variant names:

• chr7-34878090-G-T
• rs28480169
• ENST00000359791.5:c.1040G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000359791.5(NPSR1):​c.1040G>T​(p.Arg347Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,453,384 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: NPSR1 ENST00000359791.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.112
• 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13161606).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000359791.5. 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_207173.2		c.1040G>T	p.Arg347Leu	missense	Exon 9 of 9	NP_997056.1
	NPSR1	NM_001300933.2		c.1007G>T	p.Arg336Leu	missense	Exon 9 of 9	NP_001287862.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPSR1	ENST00000359791.5	TSL:1	c.1040G>T	p.Arg347Leu	missense	Exon 9 of 9	ENSP00000352839.1
	NPSR1	ENST00000531252.5	TSL:1	c.1007G>T	p.Arg336Leu	missense	Exon 9 of 9	ENSP00000433258.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1453384 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 722494

African (AFR) AF: 0.00 AC: 0 AN: 33290

American (AMR) AF: 0.00 AC: 0 AN: 44362

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25942

East Asian (EAS) AF: 0.00 AC: 0 AN: 39434

South Asian (SAS) AF: 0.00 AC: 0 AN: 84986

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53108

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5744

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1106434

Other (OTH) AF: 0.00 AC: 0 AN: 60084

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	3.1
DANN	Benign	0.80
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.041	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.11
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-0.58	N
REVEL	Benign	0.12
Sift	Uncertain	0.026	D
Sift4G	Benign	0.19	T
Polyphen		0.0080	B
Vest4		0.13
MutPred		0.63		Gain of helix (P = 0.132)
MVP		0.20
MPC		0.030
ClinPred		0.053	T
GERP RS		0.48
Mutation Taster		=96/4	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs28480169; hg19: chr7-34917702;