7-151002383-AACACACACACACACACACACACACACACACACACACACACACACAC-AACACACACACACACACACACACACACACACACACACACACACAC

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_000603.5(NOS3):​c.1752+148_1752+149delAC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.012 in 270,808 control chromosomes in the GnomAD database, including 95 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.045 ( 95 hom., cov: 0)
Exomes 𝑓: 0.0015 ( 0 hom. )

Consequence

NOS3
NM_000603.5 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.222
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0634 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NOS3NM_000603.5 linkc.1752+148_1752+149delAC intron_variant ENST00000297494.8 NP_000594.2 P29474-1
NOS3NM_001160111.1 linkc.1752+148_1752+149delAC intron_variant NP_001153583.1 P29474-2
NOS3NM_001160110.1 linkc.1752+148_1752+149delAC intron_variant NP_001153582.1 P29474-3
NOS3NM_001160109.2 linkc.1752+148_1752+149delAC intron_variant NP_001153581.1 P29474A0S0A6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NOS3ENST00000297494.8 linkc.1752+80_1752+81delAC intron_variant 1 NM_000603.5 ENSP00000297494.3 P29474-1

Frequencies

GnomAD3 genomes
AF:
0.0452
AC:
2940
AN:
65038
Hom.:
95
Cov.:
0
show subpopulations
Gnomad AFR
AF:
0.0261
Gnomad AMI
AF:
0.0161
Gnomad AMR
AF:
0.0692
Gnomad ASJ
AF:
0.0325
Gnomad EAS
AF:
0.0402
Gnomad SAS
AF:
0.0330
Gnomad FIN
AF:
0.0361
Gnomad MID
AF:
0.0357
Gnomad NFE
AF:
0.0544
Gnomad OTH
AF:
0.0505
GnomAD4 exome
AF:
0.00153
AC:
314
AN:
205714
Hom.:
0
AF XY:
0.00160
AC XY:
182
AN XY:
113892
show subpopulations
Gnomad4 AFR exome
AF:
0.000878
Gnomad4 AMR exome
AF:
0.000578
Gnomad4 ASJ exome
AF:
0.000437
Gnomad4 EAS exome
AF:
0.00200
Gnomad4 SAS exome
AF:
0.000699
Gnomad4 FIN exome
AF:
0.00285
Gnomad4 NFE exome
AF:
0.00198
Gnomad4 OTH exome
AF:
0.00118
GnomAD4 genome
AF:
0.0452
AC:
2941
AN:
65094
Hom.:
95
Cov.:
0
AF XY:
0.0447
AC XY:
1341
AN XY:
30006
show subpopulations
Gnomad4 AFR
AF:
0.0263
Gnomad4 AMR
AF:
0.0691
Gnomad4 ASJ
AF:
0.0325
Gnomad4 EAS
AF:
0.0403
Gnomad4 SAS
AF:
0.0321
Gnomad4 FIN
AF:
0.0361
Gnomad4 NFE
AF:
0.0544
Gnomad4 OTH
AF:
0.0499

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs3138808; hg19: chr7-150699471; API