7-151013540-A-C

Position:

• chr7-151013540-A-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOS3	NM_000603.5	c.3255+161A>C		intron_variant		ENST00000297494.8
ATG9B	NR_073169.1	n.2641-132T>G		intron_variant, non_coding_transcript_variant
ATG9B	NR_133652.1	n.3378-132T>G		intron_variant, non_coding_transcript_variant
ATG9B	XR_007060009.1	n.3421-132T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOS3	ENST00000297494.8	c.3255+161A>C		intron_variant		1	NM_000603.5	P1

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

Gnomad4 AFR exome AF: 0.200

Gnomad4 AMR exome AF: 0.0133

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000542

Gnomad4 FIN exome AF: 0.0000333

Gnomad4 NFE exome AF: 0.000637

Gnomad4 OTH exome AF: 0.0123

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

Gnomad4 AFR AF: 0.203

Gnomad4 AMR AF: 0.0204

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000388

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00133

Gnomad4 OTH AF: 0.0447

Alfa AF: 0.00186 Hom.: 1

Bravo AF: 0.0674

Asia WGS AF: 0.0120 AC: 43 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 15, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.9
DANN	Benign	0.45

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: rs115888621; hg19: chr7-150710628;