rs3918196

chr7-151008754-G-Achr7-151008754-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000603.5(NOS3):c.2113-176G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0775 in 657,914 control chromosomes in the GnomAD database, including 2,376 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.071 (470 hom., cov: 33)
  • Exomes 𝑓: 0.079 (1906 hom.)
• Consequence: NOS3 NM_000603.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.729

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

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 7-151008754-G-A is Benign according to our data. Variant chr7-151008754-G-A is described in ClinVar as [Benign]. Clinvar id is 1261260.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOS3	NM_000603.5	c.2113-176G>A		intron_variant		ENST00000297494.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOS3	ENST00000297494.8	c.2113-176G>A		intron_variant		1	NM_000603.5	P1
NOS3	ENST00000461406.5	c.1495-176G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0711 AC: 10822 AN: 152154 Hom.: 469 Cov.: 33

Gnomad AFR AF: 0.0510

Gnomad AMI AF: 0.236

Gnomad AMR AF: 0.0653

Gnomad ASJ AF: 0.0919

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.0861

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.0689

Gnomad OTH AF: 0.0789

GnomAD4 exome AF: 0.0794 AC: 40171 AN: 505642 Hom.: 1906 AF XY: 0.0806 AC XY: 20917 AN XY: 259540

Gnomad4 AFR exome AF: 0.0483

Gnomad4 AMR exome AF: 0.0695

Gnomad4 ASJ exome AF: 0.0905

Gnomad4 EAS exome AF: 0.185

Gnomad4 SAS exome AF: 0.106

Gnomad4 FIN exome AF: 0.0942

Gnomad4 NFE exome AF: 0.0664

Gnomad4 OTH exome AF: 0.0851

GnomAD4 genome AF: 0.0711 AC: 10828 AN: 152272 Hom.: 470 Cov.: 33 AF XY: 0.0733 AC XY: 5455 AN XY: 74446

Gnomad4 AFR AF: 0.0510

Gnomad4 AMR AF: 0.0649

Gnomad4 ASJ AF: 0.0919

Gnomad4 EAS AF: 0.168

Gnomad4 SAS AF: 0.104

Gnomad4 FIN AF: 0.0861

Gnomad4 NFE AF: 0.0689

Gnomad4 OTH AF: 0.0847

Alfa AF: 0.0700 Hom.: 375

Bravo AF: 0.0693

Asia WGS AF: 0.169 AC: 586 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 13, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	11
Dann	Benign	0.90

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs3918196; hg19: chr7-150705842;