7-151009089-G-A

Variant names:

• chr7-151009089-G-A
• rs3730006
• NM_000603.5:c.2245+27G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000603.5(NOS3):​c.2245+27G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0216 in 1,612,764 control chromosomes in the GnomAD database, including 461 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.021 (33 hom., cov: 33)
  • Exomes 𝑓: 0.022 (428 hom.)
• Consequence: NOS3 NM_000603.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.708
• Publications: 6 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=-0.88).
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.055 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.2245+27G>A		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.2245+27G>A		intron	N/A	ENSP00000297494.3
	NOS3	ENST00000461406.5	TSL:2	c.1627+27G>A		intron	N/A	ENSP00000417143.1
	NOS3	ENST00000475017.1	TSL:2	c.124+27G>A		intron	N/A	ENSP00000418245.1

Frequencies

GnomAD3 genomes AF: 0.0207 AC: 3148 AN: 152116 Hom.: 33 Cov.: 33

Gnomad AFR AF: 0.0178

Gnomad AMI AF: 0.0231

Gnomad AMR AF: 0.0276

Gnomad ASJ AF: 0.0280

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00539

Gnomad FIN AF: 0.00696

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0242

Gnomad OTH AF: 0.0460

GnomAD2 exomes AF: 0.0187 AC: 4623 AN: 246770 AF XY: 0.0189

Gnomad AFR exome AF: 0.0181

Gnomad AMR exome AF: 0.0194

Gnomad ASJ exome AF: 0.0314

Gnomad EAS exome AF: 0.0000550

Gnomad FIN exome AF: 0.00985

Gnomad NFE exome AF: 0.0248

Gnomad OTH exome AF: 0.0319

GnomAD4 exome AF: 0.0216 AC: 31617 AN: 1460530 Hom.: 428 Cov.: 32 AF XY: 0.0215 AC XY: 15633 AN XY: 726538

African (AFR) AF: 0.0196 AC: 654 AN: 33436

American (AMR) AF: 0.0204 AC: 909 AN: 44526

Ashkenazi Jewish (ASJ) AF: 0.0319 AC: 830 AN: 26034

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39682

South Asian (SAS) AF: 0.00724 AC: 624 AN: 86144

European-Finnish (FIN) AF: 0.00970 AC: 515 AN: 53100

Middle Eastern (MID) AF: 0.0602 AC: 347 AN: 5762

European-Non Finnish (NFE) AF: 0.0235 AC: 26119 AN: 1111514

Other (OTH) AF: 0.0268 AC: 1617 AN: 60332

GnomAD4 genome AF: 0.0207 AC: 3152 AN: 152234 Hom.: 33 Cov.: 33 AF XY: 0.0197 AC XY: 1470 AN XY: 74440

African (AFR) AF: 0.0178 AC: 739 AN: 41534

American (AMR) AF: 0.0275 AC: 421 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0280 AC: 97 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5178

South Asian (SAS) AF: 0.00539 AC: 26 AN: 4822

European-Finnish (FIN) AF: 0.00696 AC: 74 AN: 10626

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0242 AC: 1646 AN: 67992

Other (OTH) AF: 0.0460 AC: 97 AN: 2110

Alfa AF: 0.0238 Hom.: 19

Bravo AF: 0.0231

Asia WGS AF: 0.00520 AC: 18 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.7
DANN	Benign	0.48
PhyloP100		0.71
PromoterAI		-0.025	Neutral
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: rs3730006; hg19: chr7-150706177;