7-151002383-AACACACACACACACACACACACACACACACACACACACACACACAC-AACACACACACACAC

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1BS2

The NM_000603.5(NOS3):​c.1752+118_1752+149delACACACACACACACACACACACACACACACAC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00439 in 271,048 control chromosomes in the GnomAD database, including 26 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.015 ( 23 hom., cov: 0)
Exomes 𝑓: 0.0010 ( 3 hom. )

Consequence

NOS3
NM_000603.5 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.908
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.

BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.015 (981/65262) while in subpopulation AFR AF= 0.0519 (918/17680). AF 95% confidence interval is 0.0491. There are 23 homozygotes in gnomad4. There are 495 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
BS2
High AC in GnomAd4 at 981 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NOS3NM_000603.5 linkc.1752+118_1752+149delACACACACACACACACACACACACACACACAC intron_variant ENST00000297494.8 NP_000594.2 P29474-1
NOS3NM_001160111.1 linkc.1752+118_1752+149delACACACACACACACACACACACACACACACAC intron_variant NP_001153583.1 P29474-2
NOS3NM_001160110.1 linkc.1752+118_1752+149delACACACACACACACACACACACACACACACAC intron_variant NP_001153582.1 P29474-3
NOS3NM_001160109.2 linkc.1752+118_1752+149delACACACACACACACACACACACACACACACAC 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+111delACACACACACACACACACACACACACACACAC intron_variant 1 NM_000603.5 ENSP00000297494.3 P29474-1

Frequencies

GnomAD3 genomes
AF:
0.0151
AC:
985
AN:
65204
Hom.:
23
Cov.:
0
show subpopulations
Gnomad AFR
AF:
0.0524
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00628
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000864
Gnomad SAS
AF:
0.00190
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00714
Gnomad NFE
AF:
0.000282
Gnomad OTH
AF:
0.0152
GnomAD4 exome
AF:
0.00102
AC:
209
AN:
205786
Hom.:
3
AF XY:
0.000851
AC XY:
97
AN XY:
113938
show subpopulations
Gnomad4 AFR exome
AF:
0.0192
Gnomad4 AMR exome
AF:
0.000684
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00134
Gnomad4 SAS exome
AF:
0.000207
Gnomad4 FIN exome
AF:
0.000204
Gnomad4 NFE exome
AF:
0.000226
Gnomad4 OTH exome
AF:
0.00207
GnomAD4 genome
AF:
0.0150
AC:
981
AN:
65262
Hom.:
23
Cov.:
0
AF XY:
0.0165
AC XY:
495
AN XY:
30070
show subpopulations
Gnomad4 AFR
AF:
0.0519
Gnomad4 AMR
AF:
0.00627
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000866
Gnomad4 SAS
AF:
0.00192
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000282
Gnomad4 OTH
AF:
0.0150

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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