7-150997518-A-G

Variant names:

• chr7-150997518-A-G
• rs3918169
• NM_000603.5:c.582+593A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000603.5(NOS3):​c.582+593A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 152,006 control chromosomes in the GnomAD database, including 7,155 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.26 (7155 hom., cov: 31)
• Consequence: NOS3 NM_000603.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.341
• Publications: 2 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.508 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOS3	NM_000603.5	c.582+593A>G		intron_variant	Intron 5 of 26	ENST00000297494.8	NP_000594.2
NOS3	NM_001160111.1	c.582+593A>G		intron_variant	Intron 4 of 13		NP_001153583.1
NOS3	NM_001160110.1	c.582+593A>G		intron_variant	Intron 4 of 13		NP_001153582.1
NOS3	NM_001160109.2	c.582+593A>G		intron_variant	Intron 4 of 13		NP_001153581.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOS3	ENST00000297494.8	c.582+593A>G		intron_variant	Intron 5 of 26	1	NM_000603.5	ENSP00000297494.3
NOS3	ENST00000484524.5	c.582+593A>G		intron_variant	Intron 4 of 13	1		ENSP00000420215.1
NOS3	ENST00000467517.1	c.582+593A>G		intron_variant	Intron 4 of 13	1		ENSP00000420551.1
NOS3	ENST00000461406.5	c.-36-839A>G		intron_variant	Intron 2 of 23	2		ENSP00000417143.1

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39451 AN: 151886 Hom.: 7124 Cov.: 31

Gnomad AFR AF: 0.513

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.239

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.260 AC: 39520 AN: 152006 Hom.: 7155 Cov.: 31 AF XY: 0.257 AC XY: 19116 AN XY: 74306

African (AFR) AF: 0.514 AC: 21283 AN: 41436

American (AMR) AF: 0.170 AC: 2602 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.190 AC: 658 AN: 3468

East Asian (EAS) AF: 0.109 AC: 561 AN: 5152

South Asian (SAS) AF: 0.200 AC: 963 AN: 4812

European-Finnish (FIN) AF: 0.183 AC: 1933 AN: 10564

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.160 AC: 10851 AN: 67968

Other (OTH) AF: 0.237 AC: 501 AN: 2110

Alfa AF: 0.208 Hom.: 1149

Bravo AF: 0.268

Asia WGS AF: 0.173 AC: 604 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.92
DANN	Benign	0.42
PhyloP100		-0.34
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: rs3918169; hg19: chr7-150694606;