rs1541861

Positions:

• chr7-151000245-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000603.5(NOS3):​c.1132-253C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.696 in 151,704 control chromosomes in the GnomAD database, including 37,931 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.70 (37931 hom., cov: 30)
• Consequence: NOS3 NM_000603.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.171

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

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 7-151000245-C-A is Benign according to our data. Variant chr7-151000245-C-A is described in ClinVar as [Benign]. Clinvar id is 1178891.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.868 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOS3	NM_000603.5	c.1132-253C>A		intron_variant		ENST00000297494.8	NP_000594.2
NOS3	NM_001160111.1	c.1132-253C>A		intron_variant			NP_001153583.1
NOS3	NM_001160110.1	c.1132-253C>A		intron_variant			NP_001153582.1
NOS3	NM_001160109.2	c.1132-253C>A		intron_variant			NP_001153581.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOS3	ENST00000297494.8	c.1132-253C>A		intron_variant		1	NM_000603.5	ENSP00000297494.3
NOS3	ENST00000484524.5	c.1132-253C>A		intron_variant		1		ENSP00000420215.1
NOS3	ENST00000467517.1	c.1132-253C>A		intron_variant		1		ENSP00000420551.1
NOS3	ENST00000461406.5	c.514-253C>A		intron_variant		2		ENSP00000417143.1

Frequencies

GnomAD3 genomes AF: 0.696 AC: 105431 AN: 151586 Hom.: 37877 Cov.: 30

Gnomad AFR AF: 0.876

Gnomad AMI AF: 0.640

Gnomad AMR AF: 0.683

Gnomad ASJ AF: 0.706

Gnomad EAS AF: 0.716

Gnomad SAS AF: 0.684

Gnomad FIN AF: 0.616

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.602

Gnomad OTH AF: 0.677

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

GnomAD4 genome AF: 0.696 AC: 105538 AN: 151704 Hom.: 37931 Cov.: 30 AF XY: 0.694 AC XY: 51433 AN XY: 74126

Gnomad4 AFR AF: 0.876

Gnomad4 AMR AF: 0.684

Gnomad4 ASJ AF: 0.706

Gnomad4 EAS AF: 0.717

Gnomad4 SAS AF: 0.684

Gnomad4 FIN AF: 0.616

Gnomad4 NFE AF: 0.602

Gnomad4 OTH AF: 0.672

Alfa AF: 0.680 Hom.: 4800

Bravo AF: 0.712

Asia WGS AF: 0.689 AC: 2396 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 13, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.2
DANN	Benign	0.55

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

Publications

LitVar

Other links and lift over

dbSNP: rs1541861; hg19: chr7-150697333;