rs3730305

Variant names:

• chr7-151007312-C-A
• rs3730305
• NM_000603.5:c.2112+36C>A

Your query was ambiguous. Multiple possible variants found:

• chr7-151007312-C-A
• chr7-151007312-C-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000603.5(NOS3):​c.2112+36C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0847 in 1,551,254 control chromosomes in the GnomAD database, including 6,666 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1344 hom., cov: 33)
  • Exomes 𝑓: 0.081 (5322 hom.)
• Consequence: NOS3 NM_000603.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.45
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 7-151007312-C-A is Benign according to our data. Variant chr7-151007312-C-A is described in ClinVar as Benign. ClinVar VariationId is 1257050.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.203 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOS3	NM_000603.5	c.2112+36C>A		intron_variant	Intron 17 of 26	ENST00000297494.8	NP_000594.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOS3	ENST00000297494.8	c.2112+36C>A		intron_variant	Intron 17 of 26	1	NM_000603.5	ENSP00000297494.3
NOS3	ENST00000461406.5	c.1494+36C>A		intron_variant	Intron 14 of 23	2		ENSP00000417143.1

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18170 AN: 152074 Hom.: 1336 Cov.: 33

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.0849

Gnomad ASJ AF: 0.0945

Gnomad EAS AF: 0.0894

Gnomad SAS AF: 0.144

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0792

Gnomad OTH AF: 0.117

GnomAD2 exomes AF: 0.0977 AC: 17800 AN: 182248 AF XY: 0.0984

Gnomad AFR exome AF: 0.218

Gnomad AMR exome AF: 0.0648

Gnomad ASJ exome AF: 0.102

Gnomad EAS exome AF: 0.0896

Gnomad FIN exome AF: 0.111

Gnomad NFE exome AF: 0.0780

Gnomad OTH exome AF: 0.0895

GnomAD4 exome AF: 0.0810 AC: 113258 AN: 1399062 Hom.: 5322 Cov.: 32 AF XY: 0.0829 AC XY: 57373 AN XY: 692284

African (AFR) AF: 0.215 AC: 6904 AN: 32178

American (AMR) AF: 0.0663 AC: 2555 AN: 38516

Ashkenazi Jewish (ASJ) AF: 0.0920 AC: 2127 AN: 23126

East Asian (EAS) AF: 0.0942 AC: 3658 AN: 38818

South Asian (SAS) AF: 0.134 AC: 10725 AN: 80020

European-Finnish (FIN) AF: 0.100 AC: 3700 AN: 36908

Middle Eastern (MID) AF: 0.108 AC: 536 AN: 4954

European-Non Finnish (NFE) AF: 0.0717 AC: 77887 AN: 1086550

Other (OTH) AF: 0.0891 AC: 5166 AN: 57992

GnomAD4 genome AF: 0.120 AC: 18198 AN: 152192 Hom.: 1344 Cov.: 33 AF XY: 0.120 AC XY: 8937 AN XY: 74412

African (AFR) AF: 0.207 AC: 8577 AN: 41482

American (AMR) AF: 0.0847 AC: 1296 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0945 AC: 328 AN: 3472

East Asian (EAS) AF: 0.0892 AC: 462 AN: 5178

South Asian (SAS) AF: 0.143 AC: 693 AN: 4830

European-Finnish (FIN) AF: 0.109 AC: 1156 AN: 10610

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.0792 AC: 5384 AN: 67994

Other (OTH) AF: 0.116 AC: 246 AN: 2116

Alfa AF: 0.0944 Hom.: 663

Bravo AF: 0.121

Asia WGS AF: 0.128 AC: 444 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 13, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.11
DANN	Benign	0.51
PhyloP100		-1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs3730305; hg19: chr7-150704400;