chr7-151002383-AACACACACAC-A

Variant names:

• chr7-151002383-AACACACACAC-A
• rs3138808
• NM_000603.5:c.1752+140_1752+149delACACACACAC

Variant summary

Our verdict is Benign. The variant received -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
• 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 -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 VariationId 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.

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+140_1752+149delACACACACAC		intron	N/A	NP_000594.2
	NOS3	NM_001160111.1		c.1752+140_1752+149delACACACACAC		intron	N/A	NP_001153583.1	P29474-2
	NOS3	NM_001160110.1		c.1752+140_1752+149delACACACACAC		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+89delACACACACAC		intron	N/A	ENSP00000297494.3	P29474-1
	NOS3	ENST00000484524.5	TSL:1	c.1752+80_1752+89delACACACACAC		intron	N/A	ENSP00000420215.1	P29474-2
	NOS3	ENST00000467517.1	TSL:1	c.1752+80_1752+89delACACACACAC		intron	N/A	ENSP00000420551.1	P29474-3

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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00381 AC: 26 AN: 6832

American (AMR) AF: 0.00221 AC: 42 AN: 19000

Ashkenazi Jewish (ASJ) AF: 0.00525 AC: 36 AN: 6852

East Asian (EAS) AF: 0.00669 AC: 50 AN: 7478

South Asian (SAS) AF: 0.00822 AC: 317 AN: 38562

European-Finnish (FIN) AF: 0.00816 AC: 80 AN: 9806

Middle Eastern (MID) AF: 0.00713 AC: 6 AN: 842

European-Non Finnish (NFE) AF: 0.00856 AC: 908 AN: 106054

Other (OTH) AF: 0.00652 AC: 66 AN: 10128

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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

African (AFR) AF: 0.0538 AC: 949 AN: 17632

American (AMR) AF: 0.0685 AC: 382 AN: 5578

Ashkenazi Jewish (ASJ) AF: 0.0835 AC: 167 AN: 2000

East Asian (EAS) AF: 0.0451 AC: 104 AN: 2306

South Asian (SAS) AF: 0.0747 AC: 117 AN: 1566

European-Finnish (FIN) AF: 0.0842 AC: 233 AN: 2768

Middle Eastern (MID) AF: 0.0606 AC: 8 AN: 132

European-Non Finnish (NFE) AF: 0.0777 AC: 2475 AN: 31844

Other (OTH) AF: 0.0637 AC: 55 AN: 864

Alfa AF: 0.0199 Hom.: 86

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

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

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; COSMIC: COSV52492561;