2-168834321-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001039724.4(NOSTRIN):c.500G>A(p.Arg167Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00905 in 872,468 control chromosomes in the GnomAD database, including 420 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.033 ( 260 hom., cov: 31)

Exomes 𝑓: 0.0041 ( 160 hom. )

Consequence

NOSTRIN
NM_001039724.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.51

Publications

6 publications found

Variant links:

Genes affected

NOSTRIN (HGNC:20203): (nitric oxide synthase trafficking) Nitric oxide (NO) is a potent mediator in biologic processes such as neurotransmission, inflammatory response, and vascular homeostasis. NOSTRIN binds the enzyme responsible for NO production, endothelial NO synthase (ENOS; MIM 163729), and triggers the translocation of ENOS from the plasma membrane to vesicle-like subcellular structures, thereby attenuating ENOS-dependent NO production.[supplied by OMIM, Apr 2004]

NOSTRIN links:

SPC25 (HGNC:24031): (SPC25 component of NDC80 kinetochore complex) This gene encodes a protein that may be involved in kinetochore-microtubule interaction and spindle checkpoint activity. [provided by RefSeq, Jul 2008]

SPC25 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0012488365).

BP6

Variant 2-168834321-G-A is Benign according to our data. Variant chr2-168834321-G-A is described in ClinVar as [Benign]. Clinvar id is 767829.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOSTRIN	NM_001039724.4 link	c.500G>A	p.Arg167Gln	missense_variant	Exon 7 of 16	ENST00000317647.12	NP_001034813.2	Q8IVI9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOSTRIN	ENST00000317647.12 link	c.500G>A	p.Arg167Gln	missense_variant	Exon 7 of 16	1	NM_001039724.4	ENSP00000318921.7		Q8IVI9-1

Frequencies

GnomAD3 genomes

AF:

0.0326

AC:

4950

AN:

151992

Hom.:

255

Cov.:

show subpopulations

Gnomad AFR

AF:

0.113

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0129

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000830

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.0235

GnomAD2 exomes

AF:

0.00808

AC:

2009

AN:

248756

AF XY:

0.00631

show subpopulations

Gnomad AFR exome

AF:

0.118

Gnomad AMR exome

AF:

0.00389

Gnomad ASJ exome

AF:

0.0000994

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.000204

Gnomad OTH exome

AF:

0.00232

GnomAD4 exome

AF:

0.00407

AC:

2929

AN:

720358

Hom.:

160

Cov.:

AF XY:

0.00318

AC XY:

1224

AN XY:

384526

show subpopulations

African (AFR)

AF:

0.118

AC:

2336

AN:

19862

American (AMR)

AF:

0.00485

AC:

213

AN:

43874

Ashkenazi Jewish (ASJ)

AF:

0.0000930

AC:

AN:

21496

East Asian (EAS)

AF:

0.00

AC:

AN:

36492

South Asian (SAS)

AF:

0.000237

AC:

AN:

71662

European-Finnish (FIN)

AF:

0.0000376

AC:

AN:

53150

Middle Eastern (MID)

AF:

0.00139

AC:

AN:

4318

European-Non Finnish (NFE)

AF:

0.000138

AC:

AN:

433488

Other (OTH)

AF:

0.00814

AC:

293

AN:

36016

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

125

250

376

501

626

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0326

AC:

4966

AN:

152110

Hom.:

260

Cov.:

AF XY:

0.0312

AC XY:

2324

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.113

AC:

4699

AN:

41462

American (AMR)

AF:

0.0128

AC:

196

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.000623

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000265

AC:

AN:

67982

Other (OTH)

AF:

0.0232

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

219

438

658

877

1096

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0124

Hom.:

189

Bravo

AF:

0.0376

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.108

AC:

439

ESP6500EA

AF:

0.000238

AC:

ExAC

AF:

0.00955

AC:

1155

Asia WGS

AF:

0.00751

AC:

AN:

3478

EpiCase

AF:

0.0000546

EpiControl

AF:

0.000297

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jul 06, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.71

CADD

Benign

(source)

DANN

Benign

0.85

DEOGEN2

Benign

0.00072

.;.;T;.;.;.;.

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.45

FATHMM_MKL

Benign

0.13

LIST_S2

Uncertain

0.86

.;D;D;.;D;D;D

MetaRNN

Benign

0.0012

T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.4

N;N;N;.;.;.;.

PhyloP100

1.5

PrimateAI

Benign

0.23

PROVEAN

Benign

0.65

N;N;N;N;N;N;N

REVEL

Benign

0.070

Sift

Benign

1.0

T;T;T;T;T;T;T

Sift4G

Benign

1.0

T;T;T;T;T;T;T

Polyphen

0.0030, 0.014

.;.;B;.;.;B;.

Vest4

0.090

MVP

0.33

MPC

0.093

ClinPred

0.0053

GERP RS

0.50

Varity_R

0.036

gMVP

0.019

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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2-168834321-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over