7-151002383-AACACACACACACACACACACACACACACACACACACACACACACAC-AACACACACACACACACACACACACACACACACACAC

Position:

• chr7-151002383-AACACACACACACACACACACACACACACACACACACACACACACAC-AACACACACACACACACACACACACACACACACACAC

Variant summary

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

The NM_000603.5(NOS3):​c.1752+140_1752+149delACACACACAC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0224 in 270,678 control chromosomes in the GnomAD database, including 211 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.070 (199 hom., cov: 0)
  • Exomes 𝑓: 0.0074 (12 hom.)
• Consequence: NOS3 NM_000603.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.908

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-AACACACACAC-A is Benign according to our data. Variant chr7-151002383-AACACACACAC-A is described in ClinVar as [Benign]. Clinvar id is 1265223.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0752 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOS3	NM_000603.5	c.1752+140_1752+149delACACACACAC		intron_variant		ENST00000297494.8	NP_000594.2
NOS3	NM_001160111.1	c.1752+140_1752+149delACACACACAC		intron_variant			NP_001153583.1
NOS3	NM_001160110.1	c.1752+140_1752+149delACACACACAC		intron_variant			NP_001153582.1
NOS3	NM_001160109.2	c.1752+140_1752+149delACACACACAC		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+89delACACACACAC		intron_variant		1	NM_000603.5	ENSP00000297494.3

Frequencies

GnomAD3 genomes AF: 0.0696 AC: 4528 AN: 65066 Hom.: 199 Cov.: 0

Gnomad AFR AF: 0.0538

Gnomad AMI AF: 0.0922

Gnomad AMR AF: 0.0686

Gnomad ASJ AF: 0.0835

Gnomad EAS AF: 0.0454

Gnomad SAS AF: 0.0741

Gnomad FIN AF: 0.0842

Gnomad MID AF: 0.0643

Gnomad NFE AF: 0.0777

Gnomad OTH AF: 0.0644

GnomAD4 exome AF: 0.00745 AC: 1531 AN: 205554 Hom.: 12 AF XY: 0.00768 AC XY: 874 AN XY: 113800

Gnomad4 AFR exome AF: 0.00381

Gnomad4 AMR exome AF: 0.00221

Gnomad4 ASJ exome AF: 0.00525

Gnomad4 EAS exome AF: 0.00669

Gnomad4 SAS exome AF: 0.00822

Gnomad4 FIN exome AF: 0.00816

Gnomad4 NFE exome AF: 0.00856

Gnomad4 OTH exome AF: 0.00652

GnomAD4 genome AF: 0.0696 AC: 4530 AN: 65124 Hom.: 199 Cov.: 0 AF XY: 0.0680 AC XY: 2042 AN XY: 30014

Gnomad4 AFR AF: 0.0538

Gnomad4 AMR AF: 0.0685

Gnomad4 ASJ AF: 0.0835

Gnomad4 EAS AF: 0.0451

Gnomad4 SAS AF: 0.0747

Gnomad4 FIN AF: 0.0842

Gnomad4 NFE AF: 0.0777

Gnomad4 OTH AF: 0.0637

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 17, 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;