chr7-151006827-G-T

Variant names:

• chr7-151006827-G-T
• rs2853796
• NM_000603.5:c.1821-62G>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.50
• Publications: 24 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 -20 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 VariationId is 1230779.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.591 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000603.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOS3	NM_000603.5	MANE Select	c.1821-62G>T		intron	N/A	NP_000594.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOS3	ENST00000297494.8	TSL:1 MANE Select	c.1821-62G>T		intron	N/A	ENSP00000297494.3	P29474-1
	NOS3	ENST00000943234.1		c.1821-62G>T		intron	N/A	ENSP00000613293.1
	NOS3	ENST00000908206.1		c.1821-62G>T		intron	N/A	ENSP00000578265.1

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

African (AFR) AF: 0.463 AC: 13032 AN: 28124

American (AMR) AF: 0.680 AC: 30016 AN: 44158

Ashkenazi Jewish (ASJ) AF: 0.593 AC: 14283 AN: 24088

East Asian (EAS) AF: 0.605 AC: 23237 AN: 38422

South Asian (SAS) AF: 0.559 AC: 44371 AN: 79432

European-Finnish (FIN) AF: 0.533 AC: 28061 AN: 52642

Middle Eastern (MID) AF: 0.476 AC: 1880 AN: 3952

European-Non Finnish (NFE) AF: 0.536 AC: 462579 AN: 862680

Other (OTH) AF: 0.539 AC: 27547 AN: 51100

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

African (AFR) AF: 0.468 AC: 19421 AN: 41516

American (AMR) AF: 0.587 AC: 8985 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.596 AC: 2068 AN: 3468

East Asian (EAS) AF: 0.609 AC: 3143 AN: 5164

South Asian (SAS) AF: 0.553 AC: 2669 AN: 4824

European-Finnish (FIN) AF: 0.516 AC: 5445 AN: 10562

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.530 AC: 36005 AN: 67956

Other (OTH) AF: 0.519 AC: 1096 AN: 2110

Alfa AF: 0.509 Hom.: 14666

Bravo AF: 0.530

Asia WGS AF: 0.538 AC: 1869 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.053
DANN	Benign	0.38
PhyloP100		-2.5
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: rs2853796; hg19: chr7-150703915; COSMIC: COSV52487295; COSMIC: COSV52487295;