chr7-150992991-C-T

Position:

• chr7-150992991-C-T

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.-51-762C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.7 in 152,046 control chromosomes in the GnomAD database, including 38,247 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as protective (★).

• Frequency: Genomes: 𝑓 0.70 (38247 hom., cov: 31)
• Consequence: NOS3 NM_000603.5 intron
• Clinical Significance: protective criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.24

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=-0.86).
• BP6: Variant 7-150992991-C-T is Benign according to our data. Variant chr7-150992991-C-T is described in ClinVar as [protective]. Clinvar id is 517660.Status of the report is criteria_provided_single_submitter, 1 stars. We mark this variant Likely_benign, oryginal submissions are: {protective=1}.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.868 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOS3	NM_000603.5	c.-51-762C>T		intron_variant		ENST00000297494.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOS3	ENST00000297494.8	c.-51-762C>T		intron_variant		1	NM_000603.5	P1
NOS3	ENST00000461406.5	c.-149+1691C>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.700 AC: 106375 AN: 151928 Hom.: 38192 Cov.: 31

Gnomad AFR AF: 0.841

Gnomad AMI AF: 0.716

Gnomad AMR AF: 0.688

Gnomad ASJ AF: 0.645

Gnomad EAS AF: 0.890

Gnomad SAS AF: 0.771

Gnomad FIN AF: 0.648

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.610

Gnomad OTH AF: 0.659

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.700 AC: 106489 AN: 152046 Hom.: 38247 Cov.: 31 AF XY: 0.704 AC XY: 52330 AN XY: 74328

Gnomad4 AFR AF: 0.841

Gnomad4 AMR AF: 0.688

Gnomad4 ASJ AF: 0.645

Gnomad4 EAS AF: 0.890

Gnomad4 SAS AF: 0.771

Gnomad4 FIN AF: 0.648

Gnomad4 NFE AF: 0.610

Gnomad4 OTH AF: 0.662

Alfa AF: 0.651 Hom.: 7484

Bravo AF: 0.712

Asia WGS AF: 0.828 AC: 2879 AN: 3478

ClinVar

Significance: protective

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Metabolic syndrome, susceptibility to Benign:1

protective, criteria provided, single submitter

case-control

Laboratory of Immunology and Cellular Biotechnologies, Immanuel Kant Baltic Federal University

Jun 01, 2017

A case-control study included 70 patients with schizophrenia who had metabolic syndrome defined according to the International Diabetes Federation definition and 190 normal weight patients with schizophrenia. It has been revealed that the T allele of the T-786C (rs2070744) polymorphism in the NOS3 gene is associated with a lower risk of developing metabolic syndrome in patients with schizophrenia. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.0
DANN	Benign	0.48

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

Publications

LitVar

Other links and lift over

dbSNP: rs2070744; hg19: chr7-150690079;