Variant chr12-117220198-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_000620.5(NOS1):c.4047C>A(p.Gly1349Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000725 in 1,613,796 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00031 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00077 ( 3 hom. )

Consequence

NOS1
NM_000620.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.975

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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant 12-117220198-G-T is Benign according to our data. Variant chr12-117220198-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 791499.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.975 with no splicing effect.

BS2

High AC in GnomAd4 at 47 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOS1	NM_000620.5 linkuse as main transcript	c.4047C>A	p.Gly1349Gly	synonymous_variant	27/29	ENST00000317775.11	NP_000611.1	P29475-1B3VK56A0PJJ7B4DG68
NOS1	NM_001204218.2 linkuse as main transcript	c.4149C>A	p.Gly1383Gly	synonymous_variant	28/30		NP_001191147.1	P29475-5A0PJJ7B4DG68
NOS1	NM_001204213.2 linkuse as main transcript	c.3039C>A	p.Gly1013Gly	synonymous_variant	26/28		NP_001191142.1	P29475-3A0PJJ7B4DG68
NOS1	NM_001204214.2 linkuse as main transcript	c.3039C>A	p.Gly1013Gly	synonymous_variant	26/28		NP_001191143.1	P29475-3A0PJJ7B4DG68

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
NOS1	ENST00000317775.11 linkuse as main transcript	c.4047C>A	p.Gly1349Gly	synonymous_variant	27/29	1	NM_000620.5	ENSP00000320758.6	P29475-1
NOS1	ENST00000338101.8 linkuse as main transcript	c.4149C>A	p.Gly1383Gly	synonymous_variant	27/29	5		ENSP00000337459.4	P29475-5
NOS1	ENST00000618760.4 linkuse as main transcript	c.4149C>A	p.Gly1383Gly	synonymous_variant	28/30	5		ENSP00000477999.1	P29475-5

Frequencies

GnomAD3 genomes

AF:

0.000309

AC:

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.000529

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000200

AC:

AN:

249542

Hom.:

AF XY:

0.000207

AC XY:

AN XY:

135140

show subpopulations

Gnomad AFR exome

AF:

0.000252

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000471

Gnomad NFE exome

AF:

0.000389

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000768

AC:

1123

AN:

1461482

Hom.:

Cov.:

AF XY:

0.000759

AC XY:

552

AN XY:

727084

show subpopulations

Gnomad4 AFR exome

AF:

0.000269

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.000958

Gnomad4 OTH exome

AF:

0.000795

GnomAD4 genome

AF:

0.000309

AC:

AN:

152314

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.000216

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000529

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000478

Hom.:

Bravo

AF:

0.000283

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000709

EpiControl

AF:

0.000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

6.8

DANN

Benign

0.68

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