chr7-34778471-CA-TC

Variant names:

• chr7-34778471-CA-TC
• NM_207172.2:c.290_291delCAinsTC
• NPSR1 p.Thr97Ile

GermlineCancer (beta)

Variant summary

Our verdict is Uncertain significance.

+2 Uncertain · Warm

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received 2 classification points (ACGS-UK Somatic Oncogenicity v2025). O3_Moderate

The NM_207172.2(NPSR1):c.290_291delCAinsTC (p.Thr97Ile) variant causes a missense change. Note: allele frequency estimates from gnomAD may be inaccurate for this variant type (MNP or indel longer than 3 bp) due to technology limitations. The variant is absent from the gnomAD population database at sites with sufficient sequencing coverage. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Other variants at the same amino acid position have been reported in ClinVar (not pathogenic): p.T97I: Uncertain_significance (ClinVar VariationId 3407487, 1 star) This exact variant is curated in the UniProt human variants database as Uncertain Significance; it is also listed as a COSMIC curated somatic variant.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NPSR1 NM_207172.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.75
• 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]

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 ACGS-UK Somatic Oncogenicity v2025

Classification was made for transcript:

Our verdict: Uncertain_significance. The variant received 2 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	O3Absent or very rare in population		Absent or extremely rare in gnomAD (AC ≤ 2) — O3 moderate; GnomAD: AF = absent, AC = 0 — absent/extremely rare (O3 moderate [+2])

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.290_291delCAinsTC p.Thr97Ile	missense	N/A	Prot: NP_997055.1 UniProt:
	NPSR1 NM_001300935.2		c.290_291delCAinsTC p.Thr97Ile	missense	N/A	Prot: NP_001287864.1 UniProt:
	NPSR1 NM_207173.2		c.290_291delCAinsTC p.Thr97Ile	missense	N/A	Prot: NP_997056.1 UniProt:

NPSR1 NM_207172.2

MANE Select

HGVSc / HGVSpc.290_291delCAinsTCp.Thr97Ile

Exon rankN/A

missense

Prot: NP_997055.1UniProt: Q6W5P4-1

NPSR1 NM_001300935.2

HGVSc / HGVSpc.290_291delCAinsTCp.Thr97Ile

Exon rankN/A

missense

Prot: NP_001287864.1UniProt: Q6W5P4-3

NPSR1 NM_207173.2

HGVSc / HGVSpc.290_291delCAinsTCp.Thr97Ile

Exon rankN/A

missense

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.290_291delCAinsTC p.Thr97Ile	missense	N/A	Prot: ENSP00000353788.1 UniProt:
	NPSR1 ENST00000381539.3	TSL:1	c.290_291delCAinsTC p.Thr97Ile	missense	N/A	Prot: ENSP00000370950.3 UniProt:
	NPSR1 ENST00000359791.5	TSL:1	c.290_291delCAinsTC p.Thr97Ile	missense	N/A	Prot: ENSP00000352839.1 UniProt:

NPSR1 ENST00000360581.6

TSL:1MANE Select

HGVSc / HGVSpc.290_291delCAinsTCp.Thr97Ile

Exon rankN/A

missense

Prot: ENSP00000353788.1UniProt: Q6W5P4-1

NPSR1 ENST00000381539.3

TSL:1

HGVSc / HGVSpc.290_291delCAinsTCp.Thr97Ile

Exon rankN/A

missense

Prot: ENSP00000370950.3UniProt: Q6W5P4-3

NPSR1 ENST00000359791.5

TSL:1

HGVSc / HGVSpc.290_291delCAinsTCp.Thr97Ile

Exon rankN/A

missense

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 2 sources Large-scale international reference populations
GnomAD3 genomes	AF:	AC:	Hom:	AN:	Cov:32
GnomAD4 genome	AF:	AC:	Hom:	AN:	Cov:32

Showing 2 sources

Tested, but no data found:GnomAD4 exomeIf GnomAD4 is missing, the position is probably not covered by the project.

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
PhyloP100	Uncertain	4.8

Showing 1 of 1 scores

Splicing Scores

No splicing scores have been computed for this variant.

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

hg19: chr7-34818083;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar