NM_000603.5:c.1752+138_1752+149delACACACACACAC

Variant names:

• chr7-151002383-AACACACACACAC-A
• rs3138808
• NM_000603.5:c.1752+138_1752+149delACACACACACAC

Variant summary

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

The NM_000603.5(NOS3):​c.1752+138_1752+149delACACACACACAC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0243 in 270,622 control chromosomes in the GnomAD database, including 181 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.070 (169 hom., cov: 0)
  • Exomes 𝑓: 0.0099 (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-AACACACACACAC-A is Benign according to our data. Variant chr7-151002383-AACACACACACAC-A is described in ClinVar as [Benign]. Clinvar id is 1275619.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0797 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOS3	NM_000603.5	c.1752+138_1752+149delACACACACACAC		intron_variant	Intron 14 of 26	ENST00000297494.8	NP_000594.2
NOS3	NM_001160111.1	c.1752+138_1752+149delACACACACACAC		intron_variant	Intron 13 of 13		NP_001153583.1
NOS3	NM_001160110.1	c.1752+138_1752+149delACACACACACAC		intron_variant	Intron 13 of 13		NP_001153582.1
NOS3	NM_001160109.2	c.1752+138_1752+149delACACACACACAC		intron_variant	Intron 13 of 13		NP_001153581.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOS3	ENST00000297494.8	c.1752+80_1752+91delACACACACACAC		intron_variant	Intron 14 of 26	1	NM_000603.5	ENSP00000297494.3

Frequencies

GnomAD3 genomes AF: 0.0695 AC: 4527 AN: 65112 Hom.: 170 Cov.: 0

Gnomad AFR AF: 0.0684

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.0675

Gnomad ASJ AF: 0.0758

Gnomad EAS AF: 0.0341

Gnomad SAS AF: 0.0911

Gnomad FIN AF: 0.0794

Gnomad MID AF: 0.0643

Gnomad NFE AF: 0.0691

Gnomad OTH AF: 0.0548

GnomAD4 exome AF: 0.00993 AC: 2041 AN: 205452 Hom.: 12 AF XY: 0.0101 AC XY: 1151 AN XY: 113734

Gnomad4 AFR exome AF: 0.00660

Gnomad4 AMR exome AF: 0.00258

Gnomad4 ASJ exome AF: 0.00758

Gnomad4 EAS exome AF: 0.00695

Gnomad4 SAS exome AF: 0.0118

Gnomad4 FIN exome AF: 0.0145

Gnomad4 NFE exome AF: 0.0107

Gnomad4 OTH exome AF: 0.00939

GnomAD4 genome AF: 0.0695 AC: 4531 AN: 65170 Hom.: 169 Cov.: 0 AF XY: 0.0682 AC XY: 2046 AN XY: 30020

Gnomad4 AFR AF: 0.0685

Gnomad4 AMR AF: 0.0672

Gnomad4 ASJ AF: 0.0758

Gnomad4 EAS AF: 0.0342

Gnomad4 SAS AF: 0.0920

Gnomad4 FIN AF: 0.0794

Gnomad4 NFE AF: 0.0691

Gnomad4 OTH AF: 0.0541

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 18, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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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;