rs3729718

Variant names:

• chr17-27773118-T-G
• rs3729718
• NM_000625.4:c.1559+43A>C

Variant summary

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

The NM_000625.4(NOS2):​c.1559+43A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0038 in 1,418,948 control chromosomes in the GnomAD database, including 160 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 0.018 (85 hom., cov: 32)
  • Exomes 𝑓: 0.0020 (75 hom.)
• Consequence: NOS2 NM_000625.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.856
• Publications: 3 publications found

Genes affected

NOS2 (HGNC:7873): (nitric oxide synthase 2) Nitric oxide is a reactive free radical which acts as a biologic mediator in several processes, including neurotransmission and antimicrobial and antitumoral activities. This gene encodes a nitric oxide synthase which is expressed in liver and is inducible by a combination of lipopolysaccharide and certain cytokines. Three related pseudogenes are located within the Smith-Magenis syndrome region on chromosome 17. [provided by RefSeq, Jul 2008]

NOS2 Gene-Disease associations (from GenCC):

• schizophrenia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0615 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000625.4. 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
	NOS2	NM_000625.4	MANE Select	c.1559+43A>C		intron	N/A	NP_000616.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOS2	ENST00000313735.11	TSL:1 MANE Select	c.1559+43A>C		intron	N/A	ENSP00000327251.6
	NOS2	ENST00000886820.1		c.1559+43A>C		intron	N/A	ENSP00000556879.1
	NOS2	ENST00000646938.1		c.1556+43A>C		intron	N/A	ENSP00000494870.1

Frequencies

GnomAD3 genomes AF: 0.0182 AC: 2764 AN: 152144 Hom.: 74 Cov.: 32

Gnomad AFR AF: 0.0626

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00845

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.0124

GnomAD2 exomes AF: 0.00474 AC: 1187 AN: 250334 AF XY: 0.00336

Gnomad AFR exome AF: 0.0630

Gnomad AMR exome AF: 0.00350

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000274

Gnomad OTH exome AF: 0.00214

GnomAD4 exome AF: 0.00203 AC: 2576 AN: 1266686 Hom.: 75 Cov.: 18 AF XY: 0.00175 AC XY: 1123 AN XY: 640578

African (AFR) AF: 0.0626 AC: 1854 AN: 29626

American (AMR) AF: 0.00353 AC: 156 AN: 44224

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24892

East Asian (EAS) AF: 0.0000258 AC: 1 AN: 38724

South Asian (SAS) AF: 0.000182 AC: 15 AN: 82216

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53334

Middle Eastern (MID) AF: 0.00519 AC: 28 AN: 5390

European-Non Finnish (NFE) AF: 0.000208 AC: 194 AN: 934368

Other (OTH) AF: 0.00608 AC: 328 AN: 53912

GnomAD4 genome AF: 0.0184 AC: 2809 AN: 152262 Hom.: 85 Cov.: 32 AF XY: 0.0182 AC XY: 1354 AN XY: 74452

African (AFR) AF: 0.0635 AC: 2638 AN: 41550

American (AMR) AF: 0.00844 AC: 129 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68004

Other (OTH) AF: 0.0123 AC: 26 AN: 2112

Alfa AF: 0.00635 Hom.: 30

Bravo AF: 0.0204

Asia WGS AF: 0.00808 AC: 28 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.12
DANN	Benign	0.69
PhyloP100		-0.86
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: rs3729718; hg19: chr17-26100144;