Variant chr12-117232109-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.3258C>T(p.Asp1086=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 1,611,444 control chromosomes in the GnomAD database, including 36,971 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.23 ( 4120 hom., cov: 31)

Exomes 𝑓: 0.21 ( 32851 hom. )

Consequence

NOS1
NM_000620.5 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.259

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP6

Variant 12-117232109-G-A is Benign according to our data. Variant chr12-117232109-G-A is described in ClinVar as [Benign]. Clinvar id is 3061017.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.259 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
NOS1	NM_000620.5 linkuse as main transcript	c.3258C>T	p.Asp1086=	synonymous_variant	22/29	ENST00000317775.11	NP_000611.1
NOS1	NM_001204218.2 linkuse as main transcript	c.3360C>T	p.Asp1120=	synonymous_variant	23/30		NP_001191147.1
NOS1	NM_001204213.2 linkuse as main transcript	c.2250C>T	p.Asp750=	synonymous_variant	21/28		NP_001191142.1
NOS1	NM_001204214.2 linkuse as main transcript	c.2250C>T	p.Asp750=	synonymous_variant	21/28		NP_001191143.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOS1	ENST00000317775.11 linkuse as main transcript	c.3258C>T	p.Asp1086=	synonymous_variant	22/29	1	NM_000620.5	ENSP00000320758	P1	P29475-1
NOS1	ENST00000338101.8 linkuse as main transcript	c.3360C>T	p.Asp1120=	synonymous_variant	22/29	5		ENSP00000337459		P29475-5
NOS1	ENST00000618760.4 linkuse as main transcript	c.3360C>T	p.Asp1120=	synonymous_variant	23/30	5		ENSP00000477999		P29475-5

Frequencies

GnomAD3 genomes

AF:

0.226

AC:

34391

AN:

151852

Hom.:

4106

Cov.:

show subpopulations

Gnomad AFR

AF:

0.262

Gnomad AMI

AF:

0.194

Gnomad AMR

AF:

0.218

Gnomad ASJ

AF:

0.282

Gnomad EAS

AF:

0.325

Gnomad SAS

AF:

0.239

Gnomad FIN

AF:

0.156

Gnomad MID

AF:

0.344

Gnomad NFE

AF:

0.206

Gnomad OTH

AF:

0.247

GnomAD3 exomes

AF:

0.220

AC:

54746

AN:

248876

Hom.:

6324

AF XY:

0.222

AC XY:

30035

AN XY:

135030

show subpopulations

Gnomad AFR exome

AF:

0.261

Gnomad AMR exome

AF:

0.173

Gnomad ASJ exome

AF:

0.274

Gnomad EAS exome

AF:

0.330

Gnomad SAS exome

AF:

0.250

Gnomad FIN exome

AF:

0.165

Gnomad NFE exome

AF:

0.208

Gnomad OTH exome

AF:

0.233

GnomAD4 exome

AF:

0.209

AC:

304892

AN:

1459474

Hom.:

32851

Cov.:

AF XY:

0.211

AC XY:

153112

AN XY:

726056

show subpopulations

Gnomad4 AFR exome

AF:

0.269

Gnomad4 AMR exome

AF:

0.182

Gnomad4 ASJ exome

AF:

0.275

Gnomad4 EAS exome

AF:

0.331

Gnomad4 SAS exome

AF:

0.246

Gnomad4 FIN exome

AF:

0.166

Gnomad4 NFE exome

AF:

0.200

Gnomad4 OTH exome

AF:

0.235

GnomAD4 genome

AF:

0.227

AC:

34436

AN:

151970

Hom.:

4120

Cov.:

AF XY:

0.227

AC XY:

16856

AN XY:

74294

show subpopulations

Gnomad4 AFR

AF:

0.262

Gnomad4 AMR

AF:

0.218

Gnomad4 ASJ

AF:

0.282

Gnomad4 EAS

AF:

0.326

Gnomad4 SAS

AF:

0.238

Gnomad4 FIN

AF:

0.156

Gnomad4 NFE

AF:

0.206

Gnomad4 OTH

AF:

0.253

Alfa

AF:

0.216

Hom.:

5969

Bravo

AF:

0.230

Asia WGS

AF:

0.325

AC:

1129

AN:

3478

EpiCase

AF:

0.223

EpiControl

AF:

0.226

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

NOS1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 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

-0.59

CADD

Benign

0.73

DANN

Benign

0.75

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

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