chr7-34778526-G-A

Variant names:

• chr7-34778526-G-A
• rs324982
• NM_207172.2:c.345G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BS1 BS2

The NM_207172.2(NPSR1):​c.345G>A​(p.Thr115Thr) 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
• Publications: 2 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=-0.22).
• BP6: Variant 7-34778526-G-A is Benign according to our data. Variant chr7-34778526-G-A is described in ClinVar as Benign. ClinVar VariationId 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 11 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207172.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPSR1	NM_207172.2	MANE Select	c.345G>A	p.Thr115Thr	synonymous	Exon 3 of 9	NP_997055.1	Q6W5P4-1
	NPSR1	NM_001300935.2		c.345G>A	p.Thr115Thr	synonymous	Exon 3 of 10	NP_001287864.1	Q6W5P4-3
	NPSR1	NM_207173.2		c.345G>A	p.Thr115Thr	synonymous	Exon 3 of 9	NP_997056.1	Q6W5P4-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPSR1	ENST00000360581.6	TSL:1 MANE Select	c.345G>A	p.Thr115Thr	synonymous	Exon 3 of 9	ENSP00000353788.1	Q6W5P4-1
	NPSR1	ENST00000381539.3	TSL:1	c.345G>A	p.Thr115Thr	synonymous	Exon 3 of 10	ENSP00000370950.3	Q6W5P4-3
	NPSR1	ENST00000359791.5	TSL:1	c.345G>A	p.Thr115Thr	synonymous	Exon 3 of 9	ENSP00000352839.1	Q6W5P4-4

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

GnomAD2 exomes AF: 0.00216 AC: 542 AN: 250636 AF XY: 0.00165

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 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

African (AFR) AF: 0.0278 AC: 928 AN: 33384

American (AMR) AF: 0.00152 AC: 68 AN: 44598

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26114

East Asian (EAS) AF: 0.00 AC: 0 AN: 39654

South Asian (SAS) AF: 0.000267 AC: 23 AN: 86190

European-Finnish (FIN) AF: 0.0000375 AC: 2 AN: 53390

Middle Eastern (MID) AF: 0.00260 AC: 15 AN: 5760

European-Non Finnish (NFE) AF: 0.000130 AC: 145 AN: 1111278

Other (OTH) AF: 0.00167 AC: 101 AN: 60314

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

African (AFR) AF: 0.0267 AC: 1109 AN: 41512

American (AMR) AF: 0.00242 AC: 37 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68006

Other (OTH) AF: 0.00284 AC: 6 AN: 2110

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.22
CADD	Benign	13
DANN	Benign	0.84
PhyloP100		4.4
Mutation Taster		=95/5	polymorphism

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: rs324982; hg19: chr7-34818138;