chr7-151010400-C-T

Variant names:

• chr7-151010400-C-T
• rs743507
• NM_000603.5:c.2685+113C>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.2685+113C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.765 in 1,117,416 control chromosomes in the GnomAD database, including 327,704 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.77 (44995 hom., cov: 34)
  • Exomes 𝑓: 0.76 (282709 hom.)
• Consequence: NOS3 NM_000603.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.810
• Publications: 55 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=-0.76).
• BP6: Variant 7-151010400-C-T is Benign according to our data. Variant chr7-151010400-C-T is described in ClinVar as Benign. ClinVar VariationId is 1248545.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.812 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOS3	NM_000603.5	MANE Select	c.2685+113C>T		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.2685+113C>T		intron	N/A	ENSP00000297494.3
	NOS3	ENST00000461406.5	TSL:2	c.2067+113C>T		intron	N/A	ENSP00000417143.1
	NOS3	ENST00000475017.1	TSL:2	c.564+113C>T		intron	N/A	ENSP00000418245.1

Frequencies

GnomAD3 genomes AF: 0.767 AC: 116704 AN: 152104 Hom.: 44967 Cov.: 34

Gnomad AFR AF: 0.759

Gnomad AMI AF: 0.842

Gnomad AMR AF: 0.780

Gnomad ASJ AF: 0.732

Gnomad EAS AF: 0.787

Gnomad SAS AF: 0.833

Gnomad FIN AF: 0.834

Gnomad MID AF: 0.778

Gnomad NFE AF: 0.754

Gnomad OTH AF: 0.755

GnomAD4 exome AF: 0.764 AC: 737495 AN: 965194 Hom.: 282709 Cov.: 13 AF XY: 0.766 AC XY: 370179 AN XY: 483214

African (AFR) AF: 0.753 AC: 16453 AN: 21844

American (AMR) AF: 0.828 AC: 17974 AN: 21708

Ashkenazi Jewish (ASJ) AF: 0.716 AC: 12189 AN: 17030

East Asian (EAS) AF: 0.816 AC: 27865 AN: 34140

South Asian (SAS) AF: 0.842 AC: 49519 AN: 58788

European-Finnish (FIN) AF: 0.834 AC: 36538 AN: 43794

Middle Eastern (MID) AF: 0.777 AC: 2376 AN: 3058

European-Non Finnish (NFE) AF: 0.750 AC: 541967 AN: 722178

Other (OTH) AF: 0.765 AC: 32614 AN: 42654

GnomAD4 genome AF: 0.767 AC: 116788 AN: 152222 Hom.: 44995 Cov.: 34 AF XY: 0.771 AC XY: 57378 AN XY: 74426

African (AFR) AF: 0.758 AC: 31487 AN: 41522

American (AMR) AF: 0.780 AC: 11937 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.732 AC: 2540 AN: 3468

East Asian (EAS) AF: 0.787 AC: 4065 AN: 5168

South Asian (SAS) AF: 0.834 AC: 4030 AN: 4834

European-Finnish (FIN) AF: 0.834 AC: 8860 AN: 10618

Middle Eastern (MID) AF: 0.769 AC: 226 AN: 294

European-Non Finnish (NFE) AF: 0.754 AC: 51277 AN: 67994

Other (OTH) AF: 0.757 AC: 1598 AN: 2112

Alfa AF: 0.756 Hom.: 79943

Bravo AF: 0.764

Asia WGS AF: 0.824 AC: 2865 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

May 13, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	1.9
DANN	Benign	0.73
PhyloP100		-0.81
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: rs743507; hg19: chr7-150707488;