rs115888621

Variant names:

• chr7-151013540-A-C
• rs115888621
• NM_000603.5:c.3255+161A>C

Your query was ambiguous. Multiple possible variants found:

• chr7-151013540-A-C
• chr7-151013540-A-G

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.3255+161A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0129 in 1,125,910 control chromosomes in the GnomAD database, including 1,396 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.059 (886 hom., cov: 33)
  • Exomes 𝑓: 0.0058 (510 hom.)
• Consequence: NOS3 NM_000603.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.698
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 7-151013540-A-C is Benign according to our data. Variant chr7-151013540-A-C is described in ClinVar as Benign. ClinVar VariationId is 1221942.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.199 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.3255+161A>C		intron	N/A	NP_000594.2
	ATG9B	NR_073169.1		n.2641-132T>G		intron	N/A
	ATG9B	NR_133652.1		n.3378-132T>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOS3	ENST00000297494.8	TSL:1 MANE Select	c.3255+161A>C		intron	N/A	ENSP00000297494.3	P29474-1
	ATG9B	ENST00000605952.5	TSL:1	n.*527-132T>G		intron	N/A	ENSP00000475737.2	Q674R7-1
	ATG9B	ENST00000617967.4	TSL:1	n.2607-132T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0586 AC: 8863 AN: 151322 Hom.: 887 Cov.: 33

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0205

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000387

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.00133

Gnomad OTH AF: 0.0451

GnomAD4 exome AF: 0.00584 AC: 5694 AN: 974480 Hom.: 510 Cov.: 13 AF XY: 0.00518 AC XY: 2509 AN XY: 484344

African (AFR) AF: 0.200 AC: 4325 AN: 21618

American (AMR) AF: 0.0133 AC: 276 AN: 20678

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16780

East Asian (EAS) AF: 0.00 AC: 0 AN: 33288

South Asian (SAS) AF: 0.000542 AC: 31 AN: 57148

European-Finnish (FIN) AF: 0.0000333 AC: 1 AN: 29998

Middle Eastern (MID) AF: 0.0168 AC: 52 AN: 3088

European-Non Finnish (NFE) AF: 0.000637 AC: 477 AN: 748728

Other (OTH) AF: 0.0123 AC: 532 AN: 43154

GnomAD4 genome AF: 0.0586 AC: 8871 AN: 151430 Hom.: 886 Cov.: 33 AF XY: 0.0567 AC XY: 4196 AN XY: 73952

African (AFR) AF: 0.203 AC: 8356 AN: 41230

American (AMR) AF: 0.0204 AC: 312 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3388

East Asian (EAS) AF: 0.000388 AC: 2 AN: 5152

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4806

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10502

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.00133 AC: 90 AN: 67768

Other (OTH) AF: 0.0447 AC: 94 AN: 2104

Alfa AF: 0.00186 Hom.: 1

Bravo AF: 0.0674

Asia WGS AF: 0.0120 AC: 43 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	-0.84
CADD	Benign	2.9
DANN	Benign	0.45
PhyloP100		-0.70
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: rs115888621; hg19: chr7-150710628;