rs1008140

Variant names:

• chr7-151008522-T-C
• rs1008140
• NM_000603.5:c.2113-408T>C

Variant summary

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

The ENST00000297494.8(NOS3):​c.2113-408T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.067 in 152,258 control chromosomes in the GnomAD database, including 770 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 0.067 (770 hom., cov: 33)
• Consequence: NOS3 ENST00000297494.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.03
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000297494.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOS3	NM_000603.5	MANE Select	c.2113-408T>C		intron	N/A	NP_000594.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOS3	ENST00000297494.8	TSL:1 MANE Select	c.2113-408T>C		intron	N/A	ENSP00000297494.3
	NOS3	ENST00000461406.5	TSL:2	c.1495-408T>C		intron	N/A	ENSP00000417143.1

Frequencies

GnomAD3 genomes AF: 0.0669 AC: 10180 AN: 152140 Hom.: 766 Cov.: 33

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0281

Gnomad ASJ AF: 0.0303

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.0232

Gnomad FIN AF: 0.00245

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0196

Gnomad OTH AF: 0.0583

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

GnomAD4 genome AF: 0.0670 AC: 10208 AN: 152258 Hom.: 770 Cov.: 33 AF XY: 0.0638 AC XY: 4750 AN XY: 74448

African (AFR) AF: 0.181 AC: 7499 AN: 41520

American (AMR) AF: 0.0280 AC: 429 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0303 AC: 105 AN: 3470

East Asian (EAS) AF: 0.113 AC: 583 AN: 5174

South Asian (SAS) AF: 0.0230 AC: 111 AN: 4826

European-Finnish (FIN) AF: 0.00245 AC: 26 AN: 10614

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0195 AC: 1329 AN: 68028

Other (OTH) AF: 0.0577 AC: 122 AN: 2116

Alfa AF: 0.0305 Hom.: 106

Bravo AF: 0.0748

Asia WGS AF: 0.0810 AC: 280 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.43
DANN	Benign	0.69
PhyloP100		-2.0
PromoterAI		-0.046	Neutral
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: rs1008140; hg19: chr7-150705610;