rs199642317

Variant names:

• chr7-150993881-C-T
• rs199642317
• NM_000603.5:c.78C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_000603.5(NOS3):​c.78C>T​(p.Cys26Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000107 in 1,602,824 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000092 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00011 (0 hom.)
• Consequence: NOS3 NM_000603.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.86
• Publications: 3 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 7-150993881-C-T is Benign according to our data. Variant chr7-150993881-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 739880.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.86 with no splicing effect.
• BS2: High AC in GnomAd4 at 14 AD gene.

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.78C>T	p.Cys26Cys	synonymous	Exon 2 of 27	NP_000594.2
	NOS3	NM_001160111.1		c.78C>T	p.Cys26Cys	synonymous	Exon 1 of 14	NP_001153583.1	P29474-2
	NOS3	NM_001160110.1		c.78C>T	p.Cys26Cys	synonymous	Exon 1 of 14	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.78C>T	p.Cys26Cys	synonymous	Exon 2 of 27	ENSP00000297494.3	P29474-1
	NOS3	ENST00000484524.5	TSL:1	c.78C>T	p.Cys26Cys	synonymous	Exon 1 of 14	ENSP00000420215.1	P29474-2
	NOS3	ENST00000467517.1	TSL:1	c.78C>T	p.Cys26Cys	synonymous	Exon 1 of 14	ENSP00000420551.1	P29474-3

Frequencies

GnomAD3 genomes AF: 0.0000858 AC: 13 AN: 151564 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000243

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.000185 AC: 41 AN: 221542 AF XY: 0.000188

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000251

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000297

Gnomad OTH exome AF: 0.000364

GnomAD4 exome AF: 0.000108 AC: 157 AN: 1451142 Hom.: 0 Cov.: 31 AF XY: 0.0000901 AC XY: 65 AN XY: 721570

African (AFR) AF: 0.0000906 AC: 3 AN: 33128

American (AMR) AF: 0.000210 AC: 9 AN: 42872

Ashkenazi Jewish (ASJ) AF: 0.0000387 AC: 1 AN: 25816

East Asian (EAS) AF: 0.0000509 AC: 2 AN: 39284

South Asian (SAS) AF: 0.0000822 AC: 7 AN: 85180

European-Finnish (FIN) AF: 0.0000195 AC: 1 AN: 51198

Middle Eastern (MID) AF: 0.00167 AC: 9 AN: 5404

European-Non Finnish (NFE) AF: 0.000102 AC: 113 AN: 1108388

Other (OTH) AF: 0.000200 AC: 12 AN: 59872

GnomAD4 genome AF: 0.0000923 AC: 14 AN: 151682 Hom.: 0 Cov.: 33 AF XY: 0.000108 AC XY: 8 AN XY: 74156

African (AFR) AF: 0.0000242 AC: 1 AN: 41340

American (AMR) AF: 0.00 AC: 0 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5128

South Asian (SAS) AF: 0.00 AC: 0 AN: 4806

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10562

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 286

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 67820

Other (OTH) AF: 0.000948 AC: 2 AN: 2110

Alfa AF: 0.000136 Hom.: 0

Bravo AF: 0.0000793

ClinVar

ClinVar submissions

Significance: Likely 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
BayesDel_noAF	Benign	-0.46
CADD	Benign	7.8
DANN	Benign	0.88
PhyloP100		-1.9
PromoterAI		-0.016	Neutral
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs199642317; hg19: chr7-150690969;