chr7-151011001-A-G

Variant names:

• chr7-151011001-A-G
• rs891512
• NM_000603.5:c.2984+15A>G

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.2984+15A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.811 in 1,600,030 control chromosomes in the GnomAD database, including 529,075 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.85 (55646 hom., cov: 32)
  • Exomes 𝑓: 0.81 (473429 hom.)
• Consequence: NOS3 NM_000603.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.569
• Publications: 47 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]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 7-151011001-A-G is Benign according to our data. Variant chr7-151011001-A-G is described in ClinVar as Benign. ClinVar VariationId is 403250.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.954 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOS3	NM_000603.5	c.2984+15A>G		intron_variant	Intron 23 of 26	ENST00000297494.8	NP_000594.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOS3	ENST00000297494.8	c.2984+15A>G		intron_variant	Intron 23 of 26	1	NM_000603.5	ENSP00000297494.3

Frequencies

GnomAD3 genomes AF: 0.851 AC: 129364 AN: 152042 Hom.: 55588 Cov.: 32

Gnomad AFR AF: 0.962

Gnomad AMI AF: 0.842

Gnomad AMR AF: 0.822

Gnomad ASJ AF: 0.796

Gnomad EAS AF: 0.958

Gnomad SAS AF: 0.867

Gnomad FIN AF: 0.841

Gnomad MID AF: 0.826

Gnomad NFE AF: 0.786

Gnomad OTH AF: 0.819

GnomAD2 exomes AF: 0.842 AC: 204010 AN: 242350 AF XY: 0.835

Gnomad AFR exome AF: 0.967

Gnomad AMR exome AF: 0.884

Gnomad ASJ exome AF: 0.776

Gnomad EAS exome AF: 0.963

Gnomad FIN exome AF: 0.839

Gnomad NFE exome AF: 0.789

Gnomad OTH exome AF: 0.811

GnomAD4 exome AF: 0.807 AC: 1168478 AN: 1447870 Hom.: 473429 Cov.: 29 AF XY: 0.808 AC XY: 581967 AN XY: 720502

African (AFR) AF: 0.967 AC: 32144 AN: 33244

American (AMR) AF: 0.879 AC: 38893 AN: 44264

Ashkenazi Jewish (ASJ) AF: 0.777 AC: 20175 AN: 25964

East Asian (EAS) AF: 0.973 AC: 38471 AN: 39542

South Asian (SAS) AF: 0.877 AC: 74826 AN: 85346

European-Finnish (FIN) AF: 0.842 AC: 44681 AN: 53090

Middle Eastern (MID) AF: 0.839 AC: 4796 AN: 5714

European-Non Finnish (NFE) AF: 0.786 AC: 865648 AN: 1100774

Other (OTH) AF: 0.815 AC: 48844 AN: 59932

GnomAD4 genome AF: 0.851 AC: 129484 AN: 152160 Hom.: 55646 Cov.: 32 AF XY: 0.853 AC XY: 63431 AN XY: 74386

African (AFR) AF: 0.962 AC: 39945 AN: 41540

American (AMR) AF: 0.822 AC: 12563 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.796 AC: 2762 AN: 3472

East Asian (EAS) AF: 0.958 AC: 4941 AN: 5158

South Asian (SAS) AF: 0.867 AC: 4176 AN: 4816

European-Finnish (FIN) AF: 0.841 AC: 8903 AN: 10582

Middle Eastern (MID) AF: 0.816 AC: 240 AN: 294

European-Non Finnish (NFE) AF: 0.786 AC: 53458 AN: 67990

Other (OTH) AF: 0.820 AC: 1728 AN: 2108

Alfa AF: 0.805 Hom.: 120895

Bravo AF: 0.857

Asia WGS AF: 0.915 AC: 3180 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

May 13, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.1
DANN	Benign	0.63
PhyloP100		-0.57
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs891512; hg19: chr7-150708089; COSMIC: COSV107392333; COSMIC: COSV107392333;