dbSNP rs1800781: NOS3:c.270+42G>A (chr7-150995356-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000603.5(NOS3):c.270+42G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 1,406,146 control chromosomes in the GnomAD database, including 14,546 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1309 hom., cov: 32)

Exomes 𝑓: 0.14 ( 13237 hom. )

Consequence

NOS3
NM_000603.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.813

Publications

16 publications found

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]

NOS3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 7-150995356-G-A is Benign according to our data. Variant chr7-150995356-G-A is described in ClinVar as Benign. ClinVar VariationId is 1229830.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.151 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NOS3	NM_000603.5	MANE Select	c.270+42G>A	intron	N/A	NP_000594.2
NOS3	NM_001160111.1		c.270+42G>A	intron	N/A	NP_001153583.1	P29474-2
NOS3	NM_001160110.1		c.270+42G>A	intron	N/A	NP_001153582.1	P29474-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NOS3	ENST00000297494.8	TSL:1 MANE Select	c.270+42G>A	intron	N/A	ENSP00000297494.3	P29474-1
NOS3	ENST00000484524.5	TSL:1	c.270+42G>A	intron	N/A	ENSP00000420215.1	P29474-2
NOS3	ENST00000467517.1	TSL:1	c.270+42G>A	intron	N/A	ENSP00000420551.1	P29474-3

Frequencies

GnomAD3 genomes

AF:

0.113

AC:

17153

AN:

151960

Hom.:

1310

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0268

Gnomad AMI

AF:

0.109

Gnomad AMR

AF:

0.0953

Gnomad ASJ

AF:

0.161

Gnomad EAS

AF:

0.106

Gnomad SAS

AF:

0.155

Gnomad FIN

AF:

0.183

Gnomad MID

AF:

0.156

Gnomad NFE

AF:

0.153

Gnomad OTH

AF:

0.116

GnomAD2 exomes

AF:

0.132

AC:

28703

AN:

217458

AF XY:

0.137

show subpopulations

Gnomad AFR exome

AF:

0.0265

Gnomad AMR exome

AF:

0.0757

Gnomad ASJ exome

AF:

0.159

Gnomad EAS exome

AF:

0.105

Gnomad FIN exome

AF:

0.179

Gnomad NFE exome

AF:

0.152

Gnomad OTH exome

AF:

0.131

GnomAD4 exome

AF:

0.141

AC:

177377

AN:

1254068

Hom.:

13237

Cov.:

AF XY:

0.143

AC XY:

90055

AN XY:

629072

show subpopulations

African (AFR)

AF:

0.0247

AC:

716

AN:

29036

American (AMR)

AF:

0.0776

AC:

3255

AN:

41940

Ashkenazi Jewish (ASJ)

AF:

0.157

AC:

3784

AN:

24066

East Asian (EAS)

AF:

0.108

AC:

4026

AN:

37446

South Asian (SAS)

AF:

0.146

AC:

11646

AN:

79822

European-Finnish (FIN)

AF:

0.174

AC:

8888

AN:

51022

Middle Eastern (MID)

AF:

0.146

AC:

783

AN:

5352

European-Non Finnish (NFE)

AF:

0.147

AC:

137244

AN:

932326

Other (OTH)

AF:

0.133

AC:

7035

AN:

53058

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

7306

14612

21919

29225

36531

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4528

9056

13584

18112

22640

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.113

AC:

17143

AN:

152078

Hom.:

1309

Cov.:

AF XY:

0.114

AC XY:

8458

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.0268

AC:

1111

AN:

41476

American (AMR)

AF:

0.0951

AC:

1453

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.161

AC:

557

AN:

3470

East Asian (EAS)

AF:

0.107

AC:

550

AN:

5164

South Asian (SAS)

AF:

0.154

AC:

743

AN:

4820

European-Finnish (FIN)

AF:

0.183

AC:

1946

AN:

10622

Middle Eastern (MID)

AF:

0.154

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.153

AC:

10396

AN:

67932

Other (OTH)

AF:

0.115

AC:

243

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

754

1508

2261

3015

3769

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

202

404

606

808

1010

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.141

Hom.:

337

Bravo

AF:

0.101

Asia WGS

AF:

0.122

AC:

422

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

1.4

(source)

DANN

Benign

0.78

PhyloP100

-0.81

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over