7-151002383-AACACACACACACACACACACACACACACACACACACACACACACAC-AACACACACACACACACACACACAC

Variant names:

• chr7-151002383-AACACACACACACACACACACAC-A
• rs3138808
• NM_000603.5:c.1752+128_1752+149delACACACACACACACACACACAC

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_000603.5(NOS3):​c.1752+128_1752+149delACACACACACACACACACACAC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0188 in 270,780 control chromosomes in the GnomAD database, including 87 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.047 (70 hom., cov: 0)
  • Exomes 𝑓: 0.0099 (17 hom.)
• Consequence: NOS3 NM_000603.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.908
• Publications: 9 publications found

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

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0911 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000603.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOS3	NM_000603.5	MANE Select	c.1752+128_1752+149delACACACACACACACACACACAC		intron	N/A	NP_000594.2
	NOS3	NM_001160111.1		c.1752+128_1752+149delACACACACACACACACACACAC		intron	N/A	NP_001153583.1	P29474-2
	NOS3	NM_001160110.1		c.1752+128_1752+149delACACACACACACACACACACAC		intron	N/A	NP_001153582.1	P29474-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOS3	ENST00000297494.8	TSL:1 MANE Select	c.1752+80_1752+101delACACACACACACACACACACAC		intron	N/A	ENSP00000297494.3	P29474-1
	NOS3	ENST00000484524.5	TSL:1	c.1752+80_1752+101delACACACACACACACACACACAC		intron	N/A	ENSP00000420215.1	P29474-2
	NOS3	ENST00000467517.1	TSL:1	c.1752+80_1752+101delACACACACACACACACACACAC		intron	N/A	ENSP00000420551.1	P29474-3

Frequencies

GnomAD3 genomes AF: 0.0468 AC: 3052 AN: 65196 Hom.: 70 Cov.: 0

Gnomad AFR AF: 0.0597

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0285

Gnomad ASJ AF: 0.0727

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.0411

Gnomad FIN AF: 0.0162

Gnomad MID AF: 0.0493

Gnomad NFE AF: 0.0408

Gnomad OTH AF: 0.0490

GnomAD4 exome AF: 0.00994 AC: 2043 AN: 205526 Hom.: 17 AF XY: 0.00996 AC XY: 1133 AN XY: 113780

African (AFR) AF: 0.0103 AC: 70 AN: 6816

American (AMR) AF: 0.00231 AC: 44 AN: 19012

Ashkenazi Jewish (ASJ) AF: 0.0140 AC: 96 AN: 6852

East Asian (EAS) AF: 0.0250 AC: 187 AN: 7476

South Asian (SAS) AF: 0.0106 AC: 407 AN: 38554

European-Finnish (FIN) AF: 0.0137 AC: 134 AN: 9798

Middle Eastern (MID) AF: 0.0143 AC: 12 AN: 840

European-Non Finnish (NFE) AF: 0.00931 AC: 987 AN: 106044

Other (OTH) AF: 0.0105 AC: 106 AN: 10134

GnomAD4 genome AF: 0.0468 AC: 3052 AN: 65254 Hom.: 70 Cov.: 0 AF XY: 0.0454 AC XY: 1366 AN XY: 30062

African (AFR) AF: 0.0595 AC: 1052 AN: 17678

American (AMR) AF: 0.0285 AC: 159 AN: 5582

Ashkenazi Jewish (ASJ) AF: 0.0727 AC: 146 AN: 2008

East Asian (EAS) AF: 0.102 AC: 235 AN: 2308

South Asian (SAS) AF: 0.0415 AC: 65 AN: 1566

European-Finnish (FIN) AF: 0.0162 AC: 45 AN: 2774

Middle Eastern (MID) AF: 0.0522 AC: 7 AN: 134

European-Non Finnish (NFE) AF: 0.0408 AC: 1301 AN: 31902

Other (OTH) AF: 0.0484 AC: 42 AN: 868

Alfa AF: 0.00 Hom.: 86

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.91
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs3138808; hg19: chr7-150699471;