7-34878090-G-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_207173.2(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. 13/16 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 NM_207173.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.112

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPSR1	NM_207173.2	c.1040G>T	p.Arg347Leu	missense_variant	Exon 9 of 9		NP_997056.1
NPSR1	NM_001300933.2	c.1007G>T	p.Arg336Leu	missense_variant	Exon 9 of 9		NP_001287862.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPSR1	ENST00000359791.5	c.1040G>T	p.Arg347Leu	missense_variant	Exon 9 of 9	1		ENSP00000352839.1
NPSR1	ENST00000531252.5	c.1007G>T	p.Arg336Leu	missense_variant	Exon 9 of 9	1		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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
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;T
M_CAP	Benign	0.041	D
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-0.58	N;N
REVEL	Benign	0.12
Sift	Uncertain	0.026	D;D
Sift4G	Benign	0.19	T;T
Polyphen		0.0080	B;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

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-34917702;