rs1800781

chr7-150995356-G-A

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.270+42G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 1,406,146 control chromosomes in the GnomAD database, including 14,546 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.11 (1309 hom., cov: 32)
  • Exomes 𝑓: 0.14 (13237 hom.)
• Consequence: NOS3 NM_000603.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.813

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=-0.79).
• BP6: Variant 7-150995356-G-A is Benign according to our data. Variant chr7-150995356-G-A is described in ClinVar as [Benign]. Clinvar id is 1229830.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOS3	NM_000603.5	c.270+42G>A		intron_variant		ENST00000297494.8
NOS3	NM_001160109.2	c.270+42G>A		intron_variant
NOS3	NM_001160110.1	c.270+42G>A		intron_variant
NOS3	NM_001160111.1	c.270+42G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOS3	ENST00000297494.8	c.270+42G>A		intron_variant		1	NM_000603.5	P1
NOS3	ENST00000467517.1	c.270+42G>A		intron_variant		1
NOS3	ENST00000484524.5	c.270+42G>A		intron_variant		1
NOS3	ENST00000461406.5	c.-37+42G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17153 AN: 151960 Hom.: 1310 Cov.: 32

Gnomad AFR AF: 0.0268

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.0953

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.156

Gnomad NFE AF: 0.153

Gnomad OTH AF: 0.116

GnomAD3 exomes AF: 0.132 AC: 28703 AN: 217458 Hom.: 2076 AF XY: 0.137 AC XY: 16224 AN XY: 118344

Gnomad AFR exome AF: 0.0265

Gnomad AMR exome AF: 0.0757

Gnomad ASJ exome AF: 0.159

Gnomad EAS exome AF: 0.105

Gnomad SAS exome AF: 0.150

Gnomad FIN exome AF: 0.179

Gnomad NFE exome AF: 0.152

Gnomad OTH exome AF: 0.131

GnomAD4 exome AF: 0.141 AC: 177377 AN: 1254068 Hom.: 13237 Cov.: 16 AF XY: 0.143 AC XY: 90055 AN XY: 629072

Gnomad4 AFR exome AF: 0.0247

Gnomad4 AMR exome AF: 0.0776

Gnomad4 ASJ exome AF: 0.157

Gnomad4 EAS exome AF: 0.108

Gnomad4 SAS exome AF: 0.146

Gnomad4 FIN exome AF: 0.174

Gnomad4 NFE exome AF: 0.147

Gnomad4 OTH exome AF: 0.133

GnomAD4 genome AF: 0.113 AC: 17143 AN: 152078 Hom.: 1309 Cov.: 32 AF XY: 0.114 AC XY: 8458 AN XY: 74350

Gnomad4 AFR AF: 0.0268

Gnomad4 AMR AF: 0.0951

Gnomad4 ASJ AF: 0.161

Gnomad4 EAS AF: 0.107

Gnomad4 SAS AF: 0.154

Gnomad4 FIN AF: 0.183

Gnomad4 NFE AF: 0.153

Gnomad4 OTH AF: 0.115

Alfa AF: 0.141 Hom.: 337

Bravo AF: 0.101

Asia WGS AF: 0.122 AC: 422 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	-0.79
Cadd	Benign	1.4
Dann	Benign	0.78

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: rs1800781; hg19: chr7-150692444; COSMIC: COSV52490200;