7-34778526-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BS1 BS2

The NM_207172.2(NPSR1):c.345G>A(p.Thr115=) variant causes a synonymous change. The variant allele was found at a frequency of 0.00151 in 1,612,876 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0076 (11 hom., cov: 32)
  • Exomes 𝑓: 0.00088 (22 hom.)
• Consequence: NPSR1 NM_207172.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.42

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=-0.22).
• BP6: Variant 7-34778526-G-A is Benign according to our data. Variant chr7-34778526-G-A is described in ClinVar as [Benign]. Clinvar id is 792072.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0076 (1157/152194) while in subpopulation AFR AF= 0.0267 (1109/41512). AF 95% confidence interval is 0.0254. There are 11 homozygotes in gnomad4. There are 571 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 11 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPSR1	NM_207172.2	c.345G>A	p.Thr115=	synonymous_variant	3/9	ENST00000360581.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPSR1	ENST00000360581.6	c.345G>A	p.Thr115=	synonymous_variant	3/9	1	NM_207172.2	P1

Frequencies

GnomAD3 genomes AF: 0.00758 AC: 1153 AN: 152078 Hom.: 11 Cov.: 32

Gnomad AFR AF: 0.0267

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00242

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00216 AC: 542 AN: 250636 Hom.: 7 AF XY: 0.00165 AC XY: 224 AN XY: 135484

Gnomad AFR exome AF: 0.0281

Gnomad AMR exome AF: 0.00154

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000229

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000203

Gnomad OTH exome AF: 0.000656

GnomAD4 exome AF: 0.000878 AC: 1282 AN: 1460682 Hom.: 22 Cov.: 30 AF XY: 0.000798 AC XY: 580 AN XY: 726670

Gnomad4 AFR exome AF: 0.0278

Gnomad4 AMR exome AF: 0.00152

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000267

Gnomad4 FIN exome AF: 0.0000375

Gnomad4 NFE exome AF: 0.000130

Gnomad4 OTH exome AF: 0.00167

GnomAD4 genome AF: 0.00760 AC: 1157 AN: 152194 Hom.: 11 Cov.: 32 AF XY: 0.00767 AC XY: 571 AN XY: 74404

Gnomad4 AFR AF: 0.0267

Gnomad4 AMR AF: 0.00242

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00499 Hom.: 3

Bravo AF: 0.00890

Asia WGS AF: 0.00231 AC: 9 AN: 3478

EpiCase AF: 0.000382

EpiControl AF: 0.000654

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 08, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.22
Cadd	Benign	13
Dann	Benign	0.84

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: rs324982; hg19: chr7-34818138;