Variant rs2682826 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000620.5(NOS1):c.*276C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 1,182,334 control chromosomes in the GnomAD database, including 43,705 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.25 ( 5037 hom., cov: 33)

Exomes 𝑓: 0.27 ( 38668 hom. )

Consequence

NOS1
NM_000620.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.410

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.309 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein	UniProt
NOS1	NM_000620.5 link	c.*276C>T	3_prime_UTR_variant	29/29	ENST00000317775.11	NP_000611.1	P29475-1B3VK56A0PJJ7B4DG68
NOS1	NM_001204218.2 link	c.*276C>T	3_prime_UTR_variant	30/30		NP_001191147.1	P29475-5A0PJJ7B4DG68
NOS1	NM_001204213.2 link	c.*276C>T	3_prime_UTR_variant	28/28		NP_001191142.1	P29475-3A0PJJ7B4DG68
NOS1	NM_001204214.2 link	c.*276C>T	3_prime_UTR_variant	28/28		NP_001191143.1	P29475-3A0PJJ7B4DG68

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOS1	ENST00000317775 link	c.*276C>T		3_prime_UTR_variant	29/29	1	NM_000620.5	ENSP00000320758.6		P29475-1
NOS1	ENST00000618760 link	c.*276C>T		3_prime_UTR_variant	30/30	5		ENSP00000477999.1		P29475-5

Frequencies

GnomAD3 genomes

AF:

0.253

AC:

38483

AN:

152068

Hom.:

5030

Cov.:

show subpopulations

Gnomad AFR

AF:

0.189

Gnomad AMI

AF:

0.213

Gnomad AMR

AF:

0.249

Gnomad ASJ

AF:

0.311

Gnomad EAS

AF:

0.322

Gnomad SAS

AF:

0.251

Gnomad FIN

AF:

0.291

Gnomad MID

AF:

0.351

Gnomad NFE

AF:

0.278

Gnomad OTH

AF:

0.276

GnomAD4 exome

AF:

0.272

AC:

280463

AN:

1030148

Hom.:

38668

Cov.:

AF XY:

0.273

AC XY:

132299

AN XY:

484386

show subpopulations

Gnomad4 AFR exome

AF:

0.193

Gnomad4 AMR exome

AF:

0.244

Gnomad4 ASJ exome

AF:

0.315

Gnomad4 EAS exome

AF:

0.338

Gnomad4 SAS exome

AF:

0.249

Gnomad4 FIN exome

AF:

0.302

Gnomad4 NFE exome

AF:

0.272

Gnomad4 OTH exome

AF:

0.279

GnomAD4 genome

AF:

0.253

AC:

38511

AN:

152186

Hom.:

5037

Cov.:

AF XY:

0.256

AC XY:

19036

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.190

Gnomad4 AMR

AF:

0.248

Gnomad4 ASJ

AF:

0.311

Gnomad4 EAS

AF:

0.322

Gnomad4 SAS

AF:

0.251

Gnomad4 FIN

AF:

0.291

Gnomad4 NFE

AF:

0.278

Gnomad4 OTH

AF:

0.281

Alfa

AF:

0.274

Hom.:

8390

Bravo

AF:

0.245

Asia WGS

AF:

0.321

AC:

1114

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.52

DANN

Benign

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over