rs7830

chr7-151012483-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000603.5(NOS3):c.3106+11G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 1,607,052 control chromosomes in the GnomAD database, including 100,372 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.33 (8740 hom., cov: 32)
  • Exomes 𝑓: 0.35 (91632 hom.)
• Consequence: NOS3 NM_000603.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.566

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]

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 7-151012483-G-T is Benign according to our data. Variant chr7-151012483-G-T is described in ClinVar as [Benign]. Clinvar id is 403251.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.447 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOS3	NM_000603.5	c.3106+11G>T		intron_variant		ENST00000297494.8
ATG9B	NR_073169.1	n.3566C>A		non_coding_transcript_exon_variant	18/18
ATG9B	NR_133652.1	n.4303C>A		non_coding_transcript_exon_variant	17/17
ATG9B	XR_007060009.1	n.4346C>A		non_coding_transcript_exon_variant	15/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOS3	ENST00000297494.8	c.3106+11G>T		intron_variant		1	NM_000603.5	P1

Frequencies

GnomAD3 genomes AF: 0.327 AC: 49732 AN: 151966 Hom.: 8727 Cov.: 32

Gnomad AFR AF: 0.210

Gnomad AMI AF: 0.418

Gnomad AMR AF: 0.455

Gnomad ASJ AF: 0.309

Gnomad EAS AF: 0.391

Gnomad SAS AF: 0.418

Gnomad FIN AF: 0.422

Gnomad MID AF: 0.341

Gnomad NFE AF: 0.344

Gnomad OTH AF: 0.323

GnomAD3 exomes AF: 0.380 AC: 92833 AN: 244008 Hom.: 18978 AF XY: 0.375 AC XY: 49487 AN XY: 132044

Gnomad AFR exome AF: 0.198

Gnomad AMR exome AF: 0.589

Gnomad ASJ exome AF: 0.292

Gnomad EAS exome AF: 0.379

Gnomad SAS exome AF: 0.415

Gnomad FIN exome AF: 0.411

Gnomad NFE exome AF: 0.337

Gnomad OTH exome AF: 0.362

GnomAD4 exome AF: 0.350 AC: 508880 AN: 1454968 Hom.: 91632 Cov.: 34 AF XY: 0.351 AC XY: 253593 AN XY: 723070

Gnomad4 AFR exome AF: 0.193

Gnomad4 AMR exome AF: 0.580

Gnomad4 ASJ exome AF: 0.291

Gnomad4 EAS exome AF: 0.419

Gnomad4 SAS exome AF: 0.412

Gnomad4 FIN exome AF: 0.409

Gnomad4 NFE exome AF: 0.338

Gnomad4 OTH exome AF: 0.338

GnomAD4 genome AF: 0.327 AC: 49770 AN: 152084 Hom.: 8740 Cov.: 32 AF XY: 0.334 AC XY: 24823 AN XY: 74352

Gnomad4 AFR AF: 0.210

Gnomad4 AMR AF: 0.456

Gnomad4 ASJ AF: 0.309

Gnomad4 EAS AF: 0.391

Gnomad4 SAS AF: 0.417

Gnomad4 FIN AF: 0.422

Gnomad4 NFE AF: 0.344

Gnomad4 OTH AF: 0.321

Alfa AF: 0.328 Hom.: 11497

Bravo AF: 0.328

Asia WGS AF: 0.387 AC: 1344 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 13, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	8.0
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

Other links and lift over

dbSNP: rs7830; hg19: chr7-150709571; COSMIC: COSV52486414; COSMIC: COSV52486414;