chr7-150996342-C-G

Position:

• chr7-150996342-C-G

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.271-62C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00492 in 824,400 control chromosomes in the GnomAD database, including 239 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.011 (53 hom., cov: 7)
  • Exomes 𝑓: 0.0046 (186 hom.)
• Consequence: NOS3 NM_000603.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.377

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=-0.9).
• BP6: Variant 7-150996342-C-G is Benign according to our data. Variant chr7-150996342-C-G is described in ClinVar as [Benign]. Clinvar id is 1269294.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0735 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOS3	NM_000603.5	c.271-62C>G		intron_variant		ENST00000297494.8	NP_000594.2
NOS3	NM_001160109.2	c.271-62C>G		intron_variant			NP_001153581.1
NOS3	NM_001160110.1	c.271-62C>G		intron_variant			NP_001153582.1
NOS3	NM_001160111.1	c.271-62C>G		intron_variant			NP_001153583.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOS3	ENST00000297494.8	c.271-62C>G		intron_variant		1	NM_000603.5	ENSP00000297494	P1
NOS3	ENST00000467517.1	c.271-62C>G		intron_variant		1		ENSP00000420551
NOS3	ENST00000484524.5	c.271-62C>G		intron_variant		1		ENSP00000420215
NOS3	ENST00000461406.5	c.-37+1028C>G		intron_variant		2		ENSP00000417143

Frequencies

GnomAD3 genomes AF: 0.0110 AC: 503 AN: 45582 Hom.: 52 Cov.: 7

Gnomad AFR AF: 0.0534

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00375

Gnomad ASJ AF: 0.00242

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00420

Gnomad FIN AF: 0.000557

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00142

Gnomad OTH AF: 0.00575

GnomAD4 exome AF: 0.00456 AC: 3552 AN: 778814 Hom.: 186 AF XY: 0.00464 AC XY: 1842 AN XY: 396788

Gnomad4 AFR exome AF: 0.0769

Gnomad4 AMR exome AF: 0.00580

Gnomad4 ASJ exome AF: 0.00745

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0111

Gnomad4 FIN exome AF: 0.00141

Gnomad4 NFE exome AF: 0.00168

Gnomad4 OTH exome AF: 0.00725

GnomAD4 genome AF: 0.0111 AC: 506 AN: 45586 Hom.: 53 Cov.: 7 AF XY: 0.0120 AC XY: 257 AN XY: 21470

Gnomad4 AFR AF: 0.0538

Gnomad4 AMR AF: 0.00375

Gnomad4 ASJ AF: 0.00242

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00282

Gnomad4 FIN AF: 0.000557

Gnomad4 NFE AF: 0.00142

Gnomad4 OTH AF: 0.00560

Alfa AF: 0.0180 Hom.: 10

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 22, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.3
DANN	Benign	0.54

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: rs11974098; hg19: chr7-150693430;