Variant 12-117247465-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_000620.5(NOS1):c.2706C>T(p.His902=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 1,611,784 control chromosomes in the GnomAD database, including 82,302 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.30 ( 7477 hom., cov: 30)

Exomes 𝑓: 0.31 ( 74825 hom. )

Consequence

NOS1
NM_000620.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.37

Variant links:

Genes affected

NOS1 (HGNC:7872): (nitric oxide synthase 1) The protein encoded by this gene belongs to the family of nitric oxide synthases, which synthesize nitric oxide from L-arginine. Nitric oxide is a reactive free radical, which acts as a biologic mediator in several processes, including neurotransmission, and antimicrobial and antitumoral activities. In the brain and peripheral nervous system, nitric oxide displays many properties of a neurotransmitter, and has been implicated in neurotoxicity associated with stroke and neurodegenerative diseases, neural regulation of smooth muscle, including peristalsis, and penile erection. This protein is ubiquitously expressed, with high level of expression in skeletal muscle. Multiple transcript variants that differ in the 5' UTR have been described for this gene but the full-length nature of these transcripts is not known. Additionally, alternatively spliced transcript variants encoding different isoforms (some testis-specific) have been found for this gene.[provided by RefSeq, Feb 2011]

NOS1 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 (BayesDel_noAF=-0.76).

BP6

Variant 12-117247465-G-A is Benign according to our data. Variant chr12-117247465-G-A is described in ClinVar as [Benign]. Clinvar id is 3060800.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-1.37 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.475 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
NOS1	NM_000620.5 linkuse as main transcript	c.2706C>T	p.His902=	synonymous_variant	18/29	ENST00000317775.11
NOS1	NM_001204218.2 linkuse as main transcript	c.2808C>T	p.His936=	synonymous_variant	19/30
NOS1	NM_001204213.2 linkuse as main transcript	c.1698C>T	p.His566=	synonymous_variant	17/28
NOS1	NM_001204214.2 linkuse as main transcript	c.1698C>T	p.His566=	synonymous_variant	17/28

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOS1	ENST00000317775.11 linkuse as main transcript	c.2706C>T	p.His902=	synonymous_variant	18/29	1	NM_000620.5	P1	P29475-1
NOS1	ENST00000338101.8 linkuse as main transcript	c.2808C>T	p.His936=	synonymous_variant	18/29	5			P29475-5
NOS1	ENST00000618760.4 linkuse as main transcript	c.2808C>T	p.His936=	synonymous_variant	19/30	5			P29475-5

Frequencies

GnomAD3 genomes

AF:

0.296

AC:

44776

AN:

151302

Hom.:

7453

Cov.:

show subpopulations

Gnomad AFR

AF:

0.197

Gnomad AMI

AF:

0.346

Gnomad AMR

AF:

0.483

Gnomad ASJ

AF:

0.343

Gnomad EAS

AF:

0.490

Gnomad SAS

AF:

0.297

Gnomad FIN

AF:

0.236

Gnomad MID

AF:

0.342

Gnomad NFE

AF:

0.304

Gnomad OTH

AF:

0.329

GnomAD3 exomes

AF:

0.350

AC:

86657

AN:

247758

Hom.:

17160

AF XY:

0.341

AC XY:

45811

AN XY:

134432

show subpopulations

Gnomad AFR exome

AF:

0.193

Gnomad AMR exome

AF:

0.600

Gnomad ASJ exome

AF:

0.332

Gnomad EAS exome

AF:

0.493

Gnomad SAS exome

AF:

0.313

Gnomad FIN exome

AF:

0.248

Gnomad NFE exome

AF:

0.305

Gnomad OTH exome

AF:

0.341

GnomAD4 exome

AF:

0.313

AC:

457509

AN:

1460364

Hom.:

74825

Cov.:

AF XY:

0.313

AC XY:

227195

AN XY:

726476

show subpopulations

Gnomad4 AFR exome

AF:

0.194

Gnomad4 AMR exome

AF:

0.587

Gnomad4 ASJ exome

AF:

0.334

Gnomad4 EAS exome

AF:

0.482

Gnomad4 SAS exome

AF:

0.309

Gnomad4 FIN exome

AF:

0.254

Gnomad4 NFE exome

AF:

0.302

Gnomad4 OTH exome

AF:

0.329

GnomAD4 genome

AF:

0.296

AC:

44823

AN:

151420

Hom.:

7477

Cov.:

AF XY:

0.299

AC XY:

22117

AN XY:

73932

show subpopulations

Gnomad4 AFR

AF:

0.197

Gnomad4 AMR

AF:

0.484

Gnomad4 ASJ

AF:

0.343

Gnomad4 EAS

AF:

0.491

Gnomad4 SAS

AF:

0.297

Gnomad4 FIN

AF:

0.236

Gnomad4 NFE

AF:

0.304

Gnomad4 OTH

AF:

0.337

Alfa

AF:

0.310

Hom.:

9872

Bravo

AF:

0.311

Asia WGS

AF:

0.407

AC:

1415

AN:

3478

EpiCase

AF:

0.311

EpiControl

AF:

0.307

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

NOS1-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 18, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.017

DANN

Benign

0.87

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