chr7-150996342-C-A

Variant names:

• chr7-150996342-C-A
• rs11974098
• NM_000603.5:c.271-62C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000603.5(NOS3):​c.271-62C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000128 in 778,814 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 7)
  • Exomes 𝑓: 0.0000013 (0 hom.)
• Consequence: NOS3 NM_000603.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.377
• 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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

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.271-62C>A		intron	N/A	NP_000594.2
	NOS3	NM_001160111.1		c.271-62C>A		intron	N/A	NP_001153583.1	P29474-2
	NOS3	NM_001160110.1		c.271-62C>A		intron	N/A	NP_001153582.1	P29474-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOS3	ENST00000297494.8	TSL:1 MANE Select	c.271-62C>A		intron	N/A	ENSP00000297494.3	P29474-1
	NOS3	ENST00000484524.5	TSL:1	c.271-62C>A		intron	N/A	ENSP00000420215.1	P29474-2
	NOS3	ENST00000467517.1	TSL:1	c.271-62C>A		intron	N/A	ENSP00000420551.1	P29474-3

Frequencies

GnomAD3 genomes Cov.: 7

GnomAD4 exome AF: 0.00000128 AC: 1 AN: 778814 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 396788

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 17460

American (AMR) AF: 0.00 AC: 0 AN: 25528

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17442

East Asian (EAS) AF: 0.00 AC: 0 AN: 25662

South Asian (SAS) AF: 0.00 AC: 0 AN: 58934

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39804

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2810

European-Non Finnish (NFE) AF: 0.00000180 AC: 1 AN: 556820

Other (OTH) AF: 0.00 AC: 0 AN: 34354

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 7

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.2
DANN	Benign	0.55
PhyloP100		-0.38

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: rs11974098; hg19: chr7-150693430;