chr7-151014031-C-T

Variant names:

• chr7-151014031-C-T
• rs150714379
• NM_000603.5:c.3474C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_000603.5(NOS3):​c.3474C>T​(p.Asp1158Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000511 in 1,613,232 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00081 (2 hom., cov: 33)
  • Exomes 𝑓: 0.00048 (7 hom.)
• Consequence: NOS3 NM_000603.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.902
• Publications: 0 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]

ATG9B (HGNC:21899): (autophagy related 9B) This gene functions in the regulation of autophagy, a lysosomal degradation pathway. This gene also functions as an antisense transcript in the posttranscriptional regulation of the endothelial nitric oxide synthase 3 gene, which has 3' overlap with this gene on the opposite strand. Mutations in this gene and disruption of the autophagy process have been associated with multiple cancers. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2012]

ACMG classification

Our verdict: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.26).
• BP6: Variant 7-151014031-C-T is Benign according to our data. Variant chr7-151014031-C-T is described in ClinVar as Benign. ClinVar VariationId is 713974.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.902 with no splicing effect.
• BS2: High AC in GnomAd4 at 124 AD gene.

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.3474C>T	p.Asp1158Asp	synonymous	Exon 27 of 27	NP_000594.2
	ATG9B	NR_073169.1		n.2457+51G>A		intron	N/A
	ATG9B	NR_133652.1		n.3194+51G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOS3	ENST00000297494.8	TSL:1 MANE Select	c.3474C>T	p.Asp1158Asp	synonymous	Exon 27 of 27	ENSP00000297494.3	P29474-1
	ATG9B	ENST00000605952.5	TSL:1	n.*343+51G>A		intron	N/A	ENSP00000475737.2	Q674R7-1
	ATG9B	ENST00000617967.4	TSL:1	n.2423+51G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000815 AC: 124 AN: 152238 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.000289

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00720

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.00222 AC: 557 AN: 250674 AF XY: 0.00162

Gnomad AFR exome AF: 0.000556

Gnomad AMR exome AF: 0.0149

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000177

Gnomad OTH exome AF: 0.00163

GnomAD4 exome AF: 0.000480 AC: 701 AN: 1460876 Hom.: 7 Cov.: 35 AF XY: 0.000413 AC XY: 300 AN XY: 726594

African (AFR) AF: 0.000329 AC: 11 AN: 33462

American (AMR) AF: 0.0134 AC: 601 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.000202 AC: 8 AN: 39678

South Asian (SAS) AF: 0.000649 AC: 56 AN: 86240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53140

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00000720 AC: 8 AN: 1111440

Other (OTH) AF: 0.000282 AC: 17 AN: 60338

GnomAD4 genome AF: 0.000814 AC: 124 AN: 152356 Hom.: 2 Cov.: 33 AF XY: 0.00102 AC XY: 76 AN XY: 74498

African (AFR) AF: 0.000289 AC: 12 AN: 41584

American (AMR) AF: 0.00719 AC: 110 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68040

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.000329 Hom.: 0

Bravo AF: 0.00155

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions as Germline

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	-0.26
CADD	Benign	13
DANN	Benign	0.97
PhyloP100		0.90
Mutation Taster		=86/14	polymorphism

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: rs150714379; hg19: chr7-150711119;