NM_207172.2:c.345G>A

Variant names:

• chr7-34778526-G-A
• rs324982
• NM_207172.2:c.345G>A
• NPSR1 p.Thr115Thr

GermlineCancer (beta)

Variant summary

Our verdict is Benign.

<-10 Benign

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received -13 classification points (ACMG Germline Pathogenicity v2019). BS1BS2BP4_ModerateBP6_ModerateBP7

The NM_207172.2(NPSR1):c.345G>A (p.Thr115Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a cumulative frequency of 0.00151 (AC=2,439) in the gnomAD database across 1,612,876 control chromosomes, including 33 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.0263. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign/Likely 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 Gene-Disease associations (from GenCC):

• asthma-related traits, susceptibility to, 2

  Inheritance: AD Classification: LIMITED Submitted by: PanelApp Australia

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]

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript:

Our verdict: Benign. The variant received -13 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	BP4Computational evidence suggests no impact		Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Moderate).
	BP6Reputable source reports benign		ClinVar 1-star benign — moderate (BP6); ClinVar germline classification: Benign/Likely Benign, 1 star(s).
	BP7Synonymous variant, no splicing impact		Synonymous variant at non-conserved position with no predicted splicing impact (BP7); Synonymous at non-conserved position, no splicing concern — benign (BP7).
	BS1Allele frequency higher than expected		GnomAD effective popmax AF above BS1 threshold — greater than expected for disorder; GnomAD effective popmax AF = 0.0263 vs gene BS1 threshold 0.015.
	BS2Observed in healthy adult		≥2 homozygotes in gnomAD — observed in healthy adults (BS2); GnomAD homozygous count = 33.; Very high cumulative gnomAD AC = 2439 (any gene).

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_207172.2. You can select a different transcript below to see updated classification 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	Prot: NP_997055.1 UniProt:
	NPSR1 NM_001300935.2		c.345G>A p.Thr115Thr	synonymous	Exon 3 of 10	Prot: NP_001287864.1 UniProt:
	NPSR1 NM_207173.2		c.345G>A p.Thr115Thr	synonymous	Exon 3 of 9	Prot: NP_997056.1 UniProt:

NPSR1 NM_207172.2

MANE Select

HGVSc / HGVSpc.345G>Ap.Thr115Thr

Exon rankExon 3 of 9

synonymous

Prot: NP_997055.1UniProt: Q6W5P4-1

NPSR1 NM_001300935.2

HGVSc / HGVSpc.345G>Ap.Thr115Thr

Exon rankExon 3 of 10

synonymous

Prot: NP_001287864.1UniProt: Q6W5P4-3

NPSR1 NM_207173.2

HGVSc / HGVSpc.345G>Ap.Thr115Thr

Exon rankExon 3 of 9

synonymous

Prot: NP_997056.1UniProt: Q6W5P4-4

Ensembl Transcripts

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

NPSR1 ENST00000360581.6

TSL:1MANE Select

HGVSc / HGVSpc.345G>Ap.Thr115Thr

Exon rankExon 3 of 9

synonymous

Prot: ENSP00000353788.1UniProt: Q6W5P4-1

NPSR1 ENST00000381539.3

TSL:1

HGVSc / HGVSpc.345G>Ap.Thr115Thr

Exon rankExon 3 of 10

synonymous

Prot: ENSP00000370950.3UniProt: Q6W5P4-3

NPSR1 ENST00000359791.5

TSL:1

HGVSc / HGVSpc.345G>Ap.Thr115Thr

Exon rankExon 3 of 9

synonymous

Prot: ENSP00000352839.1UniProt: Q6W5P4-4

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 6 sources Large-scale international reference populations
GnomAD3 genomes	AF: 0.00758	AC:1153	Hom:11	AN:152078	Cov:32
GnomAD2 exomes	AF: 0.00216	AC:542	Hom:	AN:250636	Cov:
GnomAD4 exome	AF: 0.000878	AC:1282	Hom:22	AN:1460682	Cov:30
GnomAD4 genome	AF: 0.00760	AC:1157	Hom:11	AN:152194	Cov:32
TOPMed (Bravo)	AF: 0.00890	AC:2355	Hom:18	AN:264690	Cov:
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.00616	AC:647	Hom:6	AN:105046	Cov:
Local & regional cohorts 7 sources Population-specific and national genomic databases
ABraOM SABE-WGS-1171	AF: 0.00256	AC:6	Hom:0	AN:2342	Cov:
ESP6500 (Exome Variant Server)	AF: 0.00907	AC:118	Hom:	AN:13006	Cov:
GenomeAsia100K	AF: 0.00231	AC:9	Hom:	AN:3478	Cov:
Qatari Genome	AF: 0.00370	AC:7	Hom:	AN:1882	Cov:
ToMMo 61KJPN (+60KJPN MNV)	AF: 0.0000160	AC:2	Hom:0	AN:122654	Cov:
Turkish Variome	AF: 0.000708	AC:4	Hom:0	AN:5174	Cov:
UK10K	AF: 0.000132	AC:1	Hom:	AN:7562	Cov:

Showing 13 sources

Case/control cohorts

Cohort	Cases			Controls
	AF	AC	AN	AF	AC	AN
ASC(Autism)	0.00 *	0	1482	0.000139 *	1	7188
BipEx(Bipolar disorder (including schizoaffective))	0.000176	5	28376	0.0000695	2	28792
Epi25(Epilepsy)	0.00243	102	41926	0.00255	170	66776
SCHEMA(Schizophrenia)	0.00364	444	122016	0.00413	789	191060

Showing 4 cohortsAllele count / allele number. AF is computed from the counts for ASC (not provided by the source).

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Uncertain	17
BayesDel_noAF	Benign	-0.22
CADD	Benign	13
DANN	Benign	0.84
GPN-Star LLR	N/A	-2.3
GPN-Star score	N/A	2.3
Mutation Taster	N/A	95/5	polymorphism
PhyloP100	Uncertain	4.4

Showing 8 of 8 scores

Splicing Scores

Algorithm	Calibrated pred.	Score	Prediction
Pangolin (max)	Benign	0.0
SpliceAI score (max)	Benign	0.0	Details are displayed if max score is > 0.2

Showing 2 of 2 scores

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Other links and lift over

dbSNP: rs324982;

hg19: chr7-34818138;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar