Variant 7-151013712-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000603.5(NOS3):c.3256-12G>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0143 in 1,157,552 control chromosomes in the GnomAD database, including 1,400 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.054 ( 738 hom., cov: 33)

Exomes 𝑓: 0.0083 ( 662 hom. )

Consequence

NOS3
NM_000603.5 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00005298

Clinical Significance

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

Conservation

PhyloP100: -0.327

Variant links:

Genes affected

NOS3 (HGNC:7876): (nitric oxide synthase 3) Nitric oxide is a reactive free radical which acts as a biologic mediator in several processes, including neurotransmission and antimicrobial and antitumoral activities. Nitric oxide is synthesized from L-arginine by nitric oxide synthases. Variations in this gene are associated with susceptibility to coronary spasm. Alternative splicing and the use of alternative promoters results in multiple transcript variants. [provided by RefSeq, Oct 2016]

NOS3 links:

ATG9B (HGNC:21899): (autophagy related 9B) This gene functions in the regulation of autophagy, a lysosomal degradation pathway. This gene also functions as an antisense transcript in the posttranscriptional regulation of the endothelial nitric oxide synthase 3 gene, which has 3' overlap with this gene on the opposite strand. Mutations in this gene and disruption of the autophagy process have been associated with multiple cancers. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2012]

ATG9B links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 7-151013712-G-A is Benign according to our data. Variant chr7-151013712-G-A is described in ClinVar as [Benign]. Clinvar id is 1279688.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
NOS3	NM_000603.5 linkuse as main transcript	c.3256-12G>A	splice_polypyrimidine_tract_variant, intron_variant	ENST00000297494.8
ATG9B	NR_073169.1 linkuse as main transcript	n.2640+18C>T	intron_variant, non_coding_transcript_variant
ATG9B	NR_133652.1 linkuse as main transcript	n.3377+18C>T	intron_variant, non_coding_transcript_variant
ATG9B	XR_007060009.1 linkuse as main transcript	n.3420+18C>T	intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOS3	ENST00000297494.8 linkuse as main transcript	c.3256-12G>A		splice_polypyrimidine_tract_variant, intron_variant		1	NM_000603.5	P1	P29474-1

Frequencies

GnomAD3 genomes

AF:

0.0540

AC:

8124

AN:

150354

Hom.:

738

Cov.:

show subpopulations

Gnomad AFR

AF:

0.185

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0185

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000391

Gnomad SAS

AF:

0.00125

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0390

Gnomad NFE

AF:

0.00117

Gnomad OTH

AF:

0.0424

GnomAD3 exomes

AF:

0.0139

AC:

2662

AN:

191984

Hom.:

212

AF XY:

0.0101

AC XY:

1061

AN XY:

104968

show subpopulations

Gnomad AFR exome

AF:

0.197

Gnomad AMR exome

AF:

0.0103

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000119

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00117

Gnomad OTH exome

AF:

0.00780

GnomAD4 exome

AF:

0.00832

AC:

8379

AN:

1007082

Hom.:

662

Cov.:

AF XY:

0.00711

AC XY:

3608

AN XY:

507716

show subpopulations

Gnomad4 AFR exome

AF:

0.232

Gnomad4 AMR exome

AF:

0.0125

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000957

Gnomad4 SAS exome

AF:

0.000535

Gnomad4 FIN exome

AF:

0.0000251

Gnomad4 NFE exome

AF:

0.000968

Gnomad4 OTH exome

AF:

0.0163

GnomAD4 genome

AF:

0.0540

AC:

8131

AN:

150470

Hom.:

738

Cov.:

AF XY:

0.0521

AC XY:

3830

AN XY:

73540

show subpopulations

Gnomad4 AFR

AF:

0.185

Gnomad4 AMR

AF:

0.0184

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000392

Gnomad4 SAS

AF:

0.000835

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00117

Gnomad4 OTH

AF:

0.0420

Alfa

AF:

0.0205

Hom.:

Bravo

AF:

0.0612

Asia WGS

AF:

0.0110

AC:

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 05, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

6.1

DANN

Benign

0.93

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000053

dbscSNV1_RF

Benign

0.0

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