rs324981

Variant names:

• chr7-34778501-A-T
• rs324981
• NM_207172.2:c.320A>T

Your query was ambiguous. Multiple possible variants found:

• chr7-34778501-A-T
• chr7-34778501-A-G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_207172.2(NPSR1):​c.320A>T​(p.Asn107Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.45 in 1,609,296 control chromosomes in the GnomAD database, including 165,204 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.47 (17297 hom., cov: 32)
  • Exomes 𝑓: 0.45 (147907 hom.)
• Consequence: NPSR1 NM_207172.2 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 3.31
• Publications: 137 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=5.916357E-4).
• BP6: Variant 7-34778501-A-T is Benign according to our data. Variant chr7-34778501-A-T is described in ClinVar as Benign. ClinVar VariationId is 2192.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.534 is higher than 0.05.

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.320A>T	p.Asn107Ile	missense	Exon 3 of 9	NP_997055.1	Q6W5P4-1
	NPSR1	NM_001300935.2		c.320A>T	p.Asn107Ile	missense	Exon 3 of 10	NP_001287864.1	Q6W5P4-3
	NPSR1	NM_207173.2		c.320A>T	p.Asn107Ile	missense	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.320A>T	p.Asn107Ile	missense	Exon 3 of 9	ENSP00000353788.1	Q6W5P4-1
	NPSR1	ENST00000381539.3	TSL:1	c.320A>T	p.Asn107Ile	missense	Exon 3 of 10	ENSP00000370950.3	Q6W5P4-3
	NPSR1	ENST00000359791.5	TSL:1	c.320A>T	p.Asn107Ile	missense	Exon 3 of 9	ENSP00000352839.1	Q6W5P4-4

Frequencies

GnomAD3 genomes AF: 0.472 AC: 71686 AN: 151878 Hom.: 17289 Cov.: 32

Gnomad AFR AF: 0.541

Gnomad AMI AF: 0.437

Gnomad AMR AF: 0.385

Gnomad ASJ AF: 0.428

Gnomad EAS AF: 0.541

Gnomad SAS AF: 0.337

Gnomad FIN AF: 0.487

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.455

Gnomad OTH AF: 0.460

GnomAD2 exomes AF: 0.437 AC: 109388 AN: 250250 AF XY: 0.432

Gnomad AFR exome AF: 0.543

Gnomad AMR exome AF: 0.340

Gnomad ASJ exome AF: 0.433

Gnomad EAS exome AF: 0.528

Gnomad FIN exome AF: 0.475

Gnomad NFE exome AF: 0.459

Gnomad OTH exome AF: 0.432

GnomAD4 exome AF: 0.447 AC: 651975 AN: 1457300 Hom.: 147907 Cov.: 31 AF XY: 0.444 AC XY: 322307 AN XY: 725206

African (AFR) AF: 0.545 AC: 18146 AN: 33308

American (AMR) AF: 0.345 AC: 15363 AN: 44504

Ashkenazi Jewish (ASJ) AF: 0.430 AC: 11203 AN: 26072

East Asian (EAS) AF: 0.531 AC: 21007 AN: 39598

South Asian (SAS) AF: 0.331 AC: 28503 AN: 86050

European-Finnish (FIN) AF: 0.473 AC: 25222 AN: 53344

Middle Eastern (MID) AF: 0.430 AC: 2475 AN: 5752

European-Non Finnish (NFE) AF: 0.454 AC: 503250 AN: 1108464

Other (OTH) AF: 0.445 AC: 26806 AN: 60208

GnomAD4 genome AF: 0.472 AC: 71726 AN: 151996 Hom.: 17297 Cov.: 32 AF XY: 0.469 AC XY: 34855 AN XY: 74274

African (AFR) AF: 0.540 AC: 22386 AN: 41444

American (AMR) AF: 0.384 AC: 5863 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.428 AC: 1486 AN: 3468

East Asian (EAS) AF: 0.541 AC: 2787 AN: 5148

South Asian (SAS) AF: 0.337 AC: 1622 AN: 4820

European-Finnish (FIN) AF: 0.487 AC: 5145 AN: 10564

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.455 AC: 30942 AN: 67970

Other (OTH) AF: 0.459 AC: 969 AN: 2112

Alfa AF: 0.455 Hom.: 12295

Bravo AF: 0.473

TwinsUK AF: 0.446 AC: 1652

ALSPAC AF: 0.457 AC: 1762

ESP6500AA AF: 0.546 AC: 2407

ESP6500EA AF: 0.461 AC: 3962

ExAC AF: 0.446 AC: 54088

Asia WGS AF: 0.425 AC: 1477 AN: 3478

EpiCase AF: 0.452

EpiControl AF: 0.452

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	Asthma-related traits, susceptibility to, 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.021
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	13
DANN	Benign	0.77
DEOGEN2	Benign	0.048	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.91
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.068	T
MetaRNN	Benign	0.00059	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-2.5	N
PhyloP100		3.3
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	5.7	N
REVEL	Benign	0.12
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.10
MPC		0.027
ClinPred		0.0047	T
GERP RS		5.1
Varity_R		0.15
gMVP		0.10
Mutation Taster		=98/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs324981; hg19: chr7-34818113; COSMIC: COSV62208950;