rs7295972

Variant names:

• chr12-117309563-A-G
• rs7295972
• NM_000620.5:c.852+1903T>C

Your query was ambiguous. Multiple possible variants found:

• chr12-117309563-A-G
• chr12-117309563-A-T

Variant summary

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

The NM_000620.5(NOS1):​c.852+1903T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.595 in 152,090 control chromosomes in the GnomAD database, including 28,295 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 0.59 (28295 hom., cov: 32)
• Consequence: NOS1 NM_000620.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13
• Publications: 15 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.785 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOS1	NM_000620.5	MANE Select	c.852+1903T>C		intron	N/A	NP_000611.1
	NOS1	NM_001204218.2		c.852+1903T>C		intron	N/A	NP_001191147.1
	NOS1	NM_001204214.2		c.-459T>C		upstream_gene	N/A	NP_001191143.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOS1	ENST00000317775.11	TSL:1 MANE Select	c.852+1903T>C		intron	N/A	ENSP00000320758.6
	NOS1	ENST00000338101.8	TSL:5	c.852+1903T>C		intron	N/A	ENSP00000337459.4
	NOS1	ENST00000618760.4	TSL:5	c.852+1903T>C		intron	N/A	ENSP00000477999.1

Frequencies

GnomAD3 genomes AF: 0.595 AC: 90379 AN: 151972 Hom.: 28251 Cov.: 32

Gnomad AFR AF: 0.791

Gnomad AMI AF: 0.540

Gnomad AMR AF: 0.526

Gnomad ASJ AF: 0.533

Gnomad EAS AF: 0.577

Gnomad SAS AF: 0.665

Gnomad FIN AF: 0.508

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.505

Gnomad OTH AF: 0.586

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

GnomAD4 genome AF: 0.595 AC: 90483 AN: 152090 Hom.: 28295 Cov.: 32 AF XY: 0.595 AC XY: 44222 AN XY: 74340

African (AFR) AF: 0.792 AC: 32872 AN: 41520

American (AMR) AF: 0.527 AC: 8045 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.533 AC: 1848 AN: 3470

East Asian (EAS) AF: 0.577 AC: 2981 AN: 5162

South Asian (SAS) AF: 0.664 AC: 3200 AN: 4820

European-Finnish (FIN) AF: 0.508 AC: 5359 AN: 10546

Middle Eastern (MID) AF: 0.527 AC: 154 AN: 292

European-Non Finnish (NFE) AF: 0.504 AC: 34292 AN: 67978

Other (OTH) AF: 0.588 AC: 1241 AN: 2112

Alfa AF: 0.535 Hom.: 75156

Bravo AF: 0.599

Asia WGS AF: 0.630 AC: 2189 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.042
DANN	Benign	0.41
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs7295972; hg19: chr12-117747368;