rs7830

Variant names:

• chr7-151012483-G-T
• rs7830
• NM_000603.5:c.3106+11G>T

Variant summary

Our verdict is Benign. The variant received -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:3
• Conservation: PhyloP100: 0.566
• Publications: 90 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000603.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOS3	NM_000603.5	MANE Select	c.3106+11G>T		intron	N/A	NP_000594.2
	ATG9B	NR_073169.1		n.3566C>A		non_coding_transcript_exon	Exon 18 of 18
	ATG9B	NR_133652.1		n.4303C>A		non_coding_transcript_exon	Exon 17 of 17

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOS3	ENST00000297494.8	TSL:1 MANE Select	c.3106+11G>T		intron	N/A	ENSP00000297494.3	P29474-1
	ATG9B	ENST00000605952.5	TSL:1	n.*1452C>A		non_coding_transcript_exon	Exon 17 of 17	ENSP00000475737.2	Q674R7-1
	ATG9B	ENST00000605952.5	TSL:1	n.*1452C>A		3_prime_UTR	Exon 17 of 17	ENSP00000475737.2	Q674R7-1

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

GnomAD2 exomes AF: 0.380 AC: 92833 AN: 244008 AF XY: 0.375

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 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

African (AFR) AF: 0.193 AC: 6457 AN: 33434

American (AMR) AF: 0.580 AC: 25248 AN: 43568

Ashkenazi Jewish (ASJ) AF: 0.291 AC: 7585 AN: 26024

East Asian (EAS) AF: 0.419 AC: 16567 AN: 39520

South Asian (SAS) AF: 0.412 AC: 35176 AN: 85388

European-Finnish (FIN) AF: 0.409 AC: 21683 AN: 52990

Middle Eastern (MID) AF: 0.312 AC: 1795 AN: 5756

European-Non Finnish (NFE) AF: 0.338 AC: 374042 AN: 1108152

Other (OTH) AF: 0.338 AC: 20327 AN: 60136

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

African (AFR) AF: 0.210 AC: 8716 AN: 41524

American (AMR) AF: 0.456 AC: 6966 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.309 AC: 1071 AN: 3470

East Asian (EAS) AF: 0.391 AC: 2017 AN: 5156

South Asian (SAS) AF: 0.417 AC: 2013 AN: 4826

European-Finnish (FIN) AF: 0.422 AC: 4457 AN: 10556

Middle Eastern (MID) AF: 0.342 AC: 100 AN: 292

European-Non Finnish (NFE) AF: 0.344 AC: 23375 AN: 67974

Other (OTH) AF: 0.321 AC: 676 AN: 2108

Alfa AF: 0.333 Hom.: 32669

Bravo AF: 0.328

Asia WGS AF: 0.387 AC: 1344 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.0
DANN	Benign	0.75
PhyloP100		0.57
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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