7-151006827-G-T

Position:

• chr7-151006827-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000603.5(NOS3):​c.1821-62G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.542 in 1,336,704 control chromosomes in the GnomAD database, including 197,840 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.52 (21116 hom., cov: 33)
  • Exomes 𝑓: 0.54 (176724 hom.)
• Consequence: NOS3 NM_000603.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.50

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 7-151006827-G-T is Benign according to our data. Variant chr7-151006827-G-T is described in ClinVar as [Benign]. Clinvar id is 1230779.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.591 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOS3	NM_000603.5	c.1821-62G>T		intron_variant		ENST00000297494.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOS3	ENST00000297494.8	c.1821-62G>T		intron_variant		1	NM_000603.5	P1
NOS3	ENST00000461406.5	c.1203-62G>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.523 AC: 79479 AN: 151988 Hom.: 21095 Cov.: 33

Gnomad AFR AF: 0.468

Gnomad AMI AF: 0.615

Gnomad AMR AF: 0.586

Gnomad ASJ AF: 0.596

Gnomad EAS AF: 0.608

Gnomad SAS AF: 0.552

Gnomad FIN AF: 0.516

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.530

Gnomad OTH AF: 0.523

GnomAD4 exome AF: 0.544 AC: 645006 AN: 1184598 Hom.: 176724 AF XY: 0.544 AC XY: 327210 AN XY: 601612

Gnomad4 AFR exome AF: 0.463

Gnomad4 AMR exome AF: 0.680

Gnomad4 ASJ exome AF: 0.593

Gnomad4 EAS exome AF: 0.605

Gnomad4 SAS exome AF: 0.559

Gnomad4 FIN exome AF: 0.533

Gnomad4 NFE exome AF: 0.536

Gnomad4 OTH exome AF: 0.539

GnomAD4 genome AF: 0.523 AC: 79535 AN: 152106 Hom.: 21116 Cov.: 33 AF XY: 0.522 AC XY: 38804 AN XY: 74332

Gnomad4 AFR AF: 0.468

Gnomad4 AMR AF: 0.587

Gnomad4 ASJ AF: 0.596

Gnomad4 EAS AF: 0.609

Gnomad4 SAS AF: 0.553

Gnomad4 FIN AF: 0.516

Gnomad4 NFE AF: 0.530

Gnomad4 OTH AF: 0.519

Alfa AF: 0.505 Hom.: 12334

Bravo AF: 0.530

Asia WGS AF: 0.538 AC: 1869 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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	0.053
DANN	Benign	0.38

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: rs2853796; hg19: chr7-150703915; COSMIC: COSV52487295; COSMIC: COSV52487295;