chr7-34811812-A-G

Position:

chr7-34811812-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The ENST00000360581.6(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
ENST00000360581.6 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.61

Variant links:

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 links:

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]

NPSR1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 GnomAd4 at 14 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPSR1	NM_207172.2 linkuse as main transcript	c.427A>G	p.Ser143Gly	missense_variant	4/9	ENST00000360581.6	NP_997055.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NPSR1	ENST00000360581.6 linkuse as main transcript	c.427A>G	p.Ser143Gly	missense_variant	4/9	1	NM_207172.2	ENSP00000353788	P1	Q6W5P4-1

Frequencies

GnomAD3 genomes

AF:

0.00854

AC:

1294

AN:

151610

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.00171

AC XY:

232

AN XY:

135620

show subpopulations

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.:

Cov.:

AF XY:

0.000847

AC XY:

616

AN XY:

727012

show subpopulations

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.:

Cov.:

AF XY:

0.00859

AC XY:

637

AN XY:

74148

show subpopulations

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.:

Bravo

AF:

0.00994

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0300

AC:

132

ESP6500EA

AF:

0.000349

AC:

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

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 08, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.40

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.15

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.33

T;.;.;.

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.76

T;T;T;T

MetaRNN

Benign

0.015

T;T;T;T

MetaSVM

Uncertain

-0.095

MutationAssessor

Benign

2.0

M;M;.;M

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.57

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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over