rs4767523

Positions:

• chr12-117235597-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000620.5(NOS1):​c.3042-839A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 152,224 control chromosomes in the GnomAD database, including 1,356 homozygotes. 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: 𝑓 0.11 (1356 hom., cov: 32)
• Consequence: NOS1 NM_000620.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.380

Genes affected

NOS1 (HGNC:7872): (nitric oxide synthase 1) The protein encoded by this gene belongs to the family of nitric oxide synthases, which synthesize nitric oxide from L-arginine. Nitric oxide is a reactive free radical, which acts as a biologic mediator in several processes, including neurotransmission, and antimicrobial and antitumoral activities. In the brain and peripheral nervous system, nitric oxide displays many properties of a neurotransmitter, and has been implicated in neurotoxicity associated with stroke and neurodegenerative diseases, neural regulation of smooth muscle, including peristalsis, and penile erection. This protein is ubiquitously expressed, with high level of expression in skeletal muscle. Multiple transcript variants that differ in the 5' UTR have been described for this gene but the full-length nature of these transcripts is not known. Additionally, alternatively spliced transcript variants encoding different isoforms (some testis-specific) have been found for this gene.[provided by RefSeq, Feb 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.281 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOS1	NM_000620.5	c.3042-839A>C		intron_variant		ENST00000317775.11
NOS1	NM_001204213.2	c.2034-839A>C		intron_variant
NOS1	NM_001204214.2	c.2034-839A>C		intron_variant
NOS1	NM_001204218.2	c.3144-839A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOS1	ENST00000317775.11	c.3042-839A>C		intron_variant		1	NM_000620.5	P1
NOS1	ENST00000338101.8	c.3144-839A>C		intron_variant		5
NOS1	ENST00000618760.4	c.3144-839A>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17259 AN: 152106 Hom.: 1347 Cov.: 32

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.132

Gnomad AMR AF: 0.287

Gnomad ASJ AF: 0.0553

Gnomad EAS AF: 0.0237

Gnomad SAS AF: 0.0629

Gnomad FIN AF: 0.0734

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0970

Gnomad OTH AF: 0.112

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.114 AC: 17289 AN: 152224 Hom.: 1356 Cov.: 32 AF XY: 0.114 AC XY: 8482 AN XY: 74420

Gnomad4 AFR AF: 0.109

Gnomad4 AMR AF: 0.288

Gnomad4 ASJ AF: 0.0553

Gnomad4 EAS AF: 0.0235

Gnomad4 SAS AF: 0.0622

Gnomad4 FIN AF: 0.0734

Gnomad4 NFE AF: 0.0970

Gnomad4 OTH AF: 0.112

Alfa AF: 0.109 Hom.: 163

Bravo AF: 0.133

Asia WGS AF: 0.0620 AC: 217 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.68
DANN	Benign	0.44

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: rs4767523; hg19: chr12-117673402;