rs570234

Variant names:

• chr12-117333177-T-G
• rs570234
• NM_000620.5:c.-420-1688A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000620.5(NOS1):​c.-420-1688A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 152,070 control chromosomes in the GnomAD database, including 7,809 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 0.30 (7809 hom., cov: 32)
• Consequence: NOS1 NM_000620.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.205
• Publications: 5 publications found

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]

NOS1 Gene-Disease associations (from GenCC):

• idiopathic achalasia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.368 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000620.5. 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
	NOS1	NM_000620.5	MANE Select	c.-420-1688A>C		intron	N/A	NP_000611.1	P29475-1
	NOS1	NM_001204218.2		c.-420-1688A>C		intron	N/A	NP_001191147.1	P29475-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOS1	ENST00000317775.11	TSL:1 MANE Select	c.-420-1688A>C		intron	N/A	ENSP00000320758.6	P29475-1
	NOS1	ENST00000618760.4	TSL:5	c.-420-1688A>C		intron	N/A	ENSP00000477999.1	P29475-5
	NOS1	ENST00000549189.1	TSL:3	n.471-1688A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.301 AC: 45670 AN: 151950 Hom.: 7812 Cov.: 32

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.502

Gnomad AMR AF: 0.278

Gnomad ASJ AF: 0.439

Gnomad EAS AF: 0.236

Gnomad SAS AF: 0.351

Gnomad FIN AF: 0.394

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.372

Gnomad OTH AF: 0.328

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

GnomAD4 genome AF: 0.300 AC: 45665 AN: 152070 Hom.: 7809 Cov.: 32 AF XY: 0.302 AC XY: 22416 AN XY: 74334

African (AFR) AF: 0.152 AC: 6323 AN: 41500

American (AMR) AF: 0.277 AC: 4241 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.439 AC: 1525 AN: 3470

East Asian (EAS) AF: 0.235 AC: 1215 AN: 5166

South Asian (SAS) AF: 0.351 AC: 1692 AN: 4816

European-Finnish (FIN) AF: 0.394 AC: 4159 AN: 10566

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.372 AC: 25246 AN: 67950

Other (OTH) AF: 0.323 AC: 683 AN: 2112

Alfa AF: 0.351 Hom.: 3487

Bravo AF: 0.283

Asia WGS AF: 0.279 AC: 969 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.3
DANN	Benign	0.86
PhyloP100		-0.20
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: rs570234; hg19: chr12-117770982;