7-34811812-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_207172.2(NPSR1):c.427A>G(p.Ser143Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00166 in 1,613,068 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.0086 (14 hom., cov: 32)
  • Exomes 𝑓: 0.00094 (24 hom.)
• Consequence: NPSR1 NM_207172.2 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.61

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.015120894).
• BP6: Variant 7-34811812-A-G is Benign according to our data. Variant chr7-34811812-A-G is described in ClinVar as [Benign]. Clinvar id is 769708.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00858 (1302/151726) while in subpopulation AFR AF= 0.0303 (1252/41252). AF 95% confidence interval is 0.029. There are 14 homozygotes in gnomad4. There are 637 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 14 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPSR1	NM_207172.2	c.427A>G	p.Ser143Gly	missense_variant	4/9	ENST00000360581.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPSR1	ENST00000360581.6	c.427A>G	p.Ser143Gly	missense_variant	4/9	1	NM_207172.2	P1

Frequencies

GnomAD3 genomes AF: 0.00854 AC: 1294 AN: 151610 Hom.: 14 Cov.: 32

Gnomad AFR AF: 0.0302

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00263

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: 0.0000588

Gnomad OTH AF: 0.00288

GnomAD3 exomes AF: 0.00232 AC: 582 AN: 250864 Hom.: 6 AF XY: 0.00171 AC XY: 232 AN XY: 135620

Gnomad AFR exome AF: 0.0304

Gnomad AMR exome AF: 0.00166

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000164

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000194

Gnomad OTH exome AF: 0.000820

GnomAD4 exome AF: 0.000942 AC: 1377 AN: 1461342 Hom.: 24 Cov.: 30 AF XY: 0.000847 AC XY: 616 AN XY: 727012

Gnomad4 AFR exome AF: 0.0309

Gnomad4 AMR exome AF: 0.00161

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000162

Gnomad4 FIN exome AF: 0.0000374

Gnomad4 NFE exome AF: 0.000114

Gnomad4 OTH exome AF: 0.00189

GnomAD4 genome AF: 0.00858 AC: 1302 AN: 151726 Hom.: 14 Cov.: 32 AF XY: 0.00859 AC XY: 637 AN XY: 74148

Gnomad4 AFR AF: 0.0303

Gnomad4 AMR AF: 0.00262

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.00285

Alfa AF: 0.00141 Hom.: 1

Bravo AF: 0.00994

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0300 AC: 132

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.00297 AC: 361

EpiCase AF: 0.000382

EpiControl AF: 0.000593

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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.15
Cadd	Uncertain	23
Dann	Uncertain	1.0
DEOGEN2	Benign	0.33	T;.;.;.
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.76	T;T;T;T
MetaRNN	Benign	0.015	T;T;T;T
MetaSVM	Uncertain	-0.095	T
MutationAssessor	Benign	2.0	M;M;.;M
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-3.5	D;D;D;D
REVEL	Uncertain	0.56
Sift	Uncertain	0.0010	D;D;D;D
Sift4G	Uncertain	0.014	D;D;D;D
Polyphen		1.0	D;D;D;D
Vest4		0.76
MVP		0.95
MPC		0.030
ClinPred		0.056	T
GERP RS		4.2
Varity_R		0.73
gMVP		0.83

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: rs325465; hg19: chr7-34851424;