chr7-150992991-C-T

Variant names:

• chr7-150992991-C-T
• rs2070744
• NM_000603.5:c.-51-762C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong 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
• Publications: 1094 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.868 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOS3	NM_000603.5	MANE Select	c.-51-762C>T		intron	N/A	NP_000594.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOS3	ENST00000297494.8	TSL:1 MANE Select	c.-51-762C>T		intron	N/A	ENSP00000297494.3
	NOS3	ENST00000461406.5	TSL:2	c.-149+1691C>T		intron	N/A	ENSP00000417143.1

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

African (AFR) AF: 0.841 AC: 34896 AN: 41488

American (AMR) AF: 0.688 AC: 10518 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.645 AC: 2239 AN: 3470

East Asian (EAS) AF: 0.890 AC: 4571 AN: 5138

South Asian (SAS) AF: 0.771 AC: 3717 AN: 4820

European-Finnish (FIN) AF: 0.648 AC: 6864 AN: 10588

Middle Eastern (MID) AF: 0.629 AC: 185 AN: 294

European-Non Finnish (NFE) AF: 0.610 AC: 41453 AN: 67948

Other (OTH) AF: 0.662 AC: 1396 AN: 2110

Alfa AF: 0.638 Hom.: 48710

Bravo AF: 0.712

Asia WGS AF: 0.828 AC: 2879 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: protective

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	-	Metabolic syndrome, susceptibility to (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.0
DANN	Benign	0.48
PhyloP100		-1.2
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: rs2070744; hg19: chr7-150690079;