chr7-151005344-A-T

Variant names:

• chr7-151005344-A-T
• rs3918186
• NM_000603.5:c.1753-1083A>T

Variant summary

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

The NM_000603.5(NOS3):​c.1753-1083A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 152,216 control chromosomes in the GnomAD database, including 1,290 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 0.12 (1290 hom., cov: 33)
• Consequence: NOS3 NM_000603.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.198
• Publications: 26 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOS3	NM_000603.5	c.1753-1083A>T		intron_variant	Intron 14 of 26	ENST00000297494.8	NP_000594.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOS3	ENST00000297494.8	c.1753-1083A>T		intron_variant	Intron 14 of 26	1	NM_000603.5	ENSP00000297494.3
NOS3	ENST00000461406.5	c.1135-1083A>T		intron_variant	Intron 11 of 23	2		ENSP00000417143.1

Frequencies

GnomAD3 genomes AF: 0.118 AC: 17893 AN: 152098 Hom.: 1286 Cov.: 33

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.0253

Gnomad AMR AF: 0.0857

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.0894

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0817

Gnomad OTH AF: 0.122

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

GnomAD4 genome AF: 0.118 AC: 17917 AN: 152216 Hom.: 1290 Cov.: 33 AF XY: 0.119 AC XY: 8869 AN XY: 74426

African (AFR) AF: 0.193 AC: 8022 AN: 41512

American (AMR) AF: 0.0855 AC: 1308 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 353 AN: 3468

East Asian (EAS) AF: 0.0894 AC: 463 AN: 5178

South Asian (SAS) AF: 0.150 AC: 725 AN: 4824

European-Finnish (FIN) AF: 0.111 AC: 1174 AN: 10598

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

European-Non Finnish (NFE) AF: 0.0818 AC: 5561 AN: 68024

Other (OTH) AF: 0.121 AC: 255 AN: 2108

Alfa AF: 0.101 Hom.: 127

Bravo AF: 0.117

Asia WGS AF: 0.131 AC: 453 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.7
DANN	Benign	0.79
PhyloP100		-0.20
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: rs3918186; hg19: chr7-150702432;