7-151002383-AACACACACACACACACACACACACACACACACACACACACACACAC-AACACACACACACACACACACACACACACACACACACACAC

Position:

• chr7-151002383-AACACACACACACACACACACACACACACACACACACACACACACAC-AACACACACACACACACACACACACACACACACACACACAC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_000603.5(NOS3):​c.1752+144_1752+149delACACAC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0186 in 270,716 control chromosomes in the GnomAD database, including 188 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.061 (184 hom., cov: 0)
  • Exomes 𝑓: 0.0053 (4 hom.)
• Consequence: NOS3 NM_000603.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.192

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 -10 ACMG points.

• BP6: Variant 7-151002383-AACACAC-A is Benign according to our data. Variant chr7-151002383-AACACAC-A is described in ClinVar as [Benign]. Clinvar id is 1261942.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0691 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOS3	NM_000603.5	c.1752+144_1752+149delACACAC		intron_variant		ENST00000297494.8	NP_000594.2
NOS3	NM_001160111.1	c.1752+144_1752+149delACACAC		intron_variant			NP_001153583.1
NOS3	NM_001160110.1	c.1752+144_1752+149delACACAC		intron_variant			NP_001153582.1
NOS3	NM_001160109.2	c.1752+144_1752+149delACACAC		intron_variant			NP_001153581.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOS3	ENST00000297494.8	c.1752+80_1752+85delACACAC		intron_variant		1	NM_000603.5	ENSP00000297494.3

Frequencies

GnomAD3 genomes AF: 0.0607 AC: 3946 AN: 65048 Hom.: 184 Cov.: 0

Gnomad AFR AF: 0.0394

Gnomad AMI AF: 0.0926

Gnomad AMR AF: 0.0709

Gnomad ASJ AF: 0.0623

Gnomad EAS AF: 0.0402

Gnomad SAS AF: 0.0425

Gnomad FIN AF: 0.0683

Gnomad MID AF: 0.121

Gnomad NFE AF: 0.0715

Gnomad OTH AF: 0.0618

GnomAD4 exome AF: 0.00534 AC: 1097 AN: 205610 Hom.: 4 AF XY: 0.00545 AC XY: 621 AN XY: 113842

Gnomad4 AFR exome AF: 0.00264

Gnomad4 AMR exome AF: 0.00200

Gnomad4 ASJ exome AF: 0.00335

Gnomad4 EAS exome AF: 0.00388

Gnomad4 SAS exome AF: 0.00480

Gnomad4 FIN exome AF: 0.00713

Gnomad4 NFE exome AF: 0.00640

Gnomad4 OTH exome AF: 0.00474

GnomAD4 genome AF: 0.0607 AC: 3950 AN: 65106 Hom.: 184 Cov.: 0 AF XY: 0.0598 AC XY: 1794 AN XY: 30008

Gnomad4 AFR AF: 0.0395

Gnomad4 AMR AF: 0.0708

Gnomad4 ASJ AF: 0.0623

Gnomad4 EAS AF: 0.0399

Gnomad4 SAS AF: 0.0429

Gnomad4 FIN AF: 0.0683

Gnomad4 NFE AF: 0.0715

Gnomad4 OTH AF: 0.0622

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

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3138808; hg19: chr7-150699471;