rs11080344

Variant names:

• chr17-27777485-T-C
• rs11080344
• NM_000625.4:c.1281+1205A>G

Your query was ambiguous. Multiple possible variants found:

• chr17-27777485-T-C
• chr17-27777485-T-G

Variant summary

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

The NM_000625.4(NOS2):​c.1281+1205A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.566 in 152,096 control chromosomes in the GnomAD database, including 25,840 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 0.57 (25840 hom., cov: 32)
• Consequence: NOS2 NM_000625.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.972
• Publications: 23 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.758 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOS2	NM_000625.4	c.1281+1205A>G		intron_variant	Intron 11 of 26	ENST00000313735.11	NP_000616.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOS2	ENST00000313735.11	c.1281+1205A>G		intron_variant	Intron 11 of 26	1	NM_000625.4	ENSP00000327251.6

Frequencies

GnomAD3 genomes AF: 0.566 AC: 85947 AN: 151982 Hom.: 25785 Cov.: 32

Gnomad AFR AF: 0.765

Gnomad AMI AF: 0.586

Gnomad AMR AF: 0.559

Gnomad ASJ AF: 0.528

Gnomad EAS AF: 0.590

Gnomad SAS AF: 0.650

Gnomad FIN AF: 0.453

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.457

Gnomad OTH AF: 0.557

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

GnomAD4 genome AF: 0.566 AC: 86050 AN: 152096 Hom.: 25840 Cov.: 32 AF XY: 0.568 AC XY: 42180 AN XY: 74324

African (AFR) AF: 0.766 AC: 31773 AN: 41504

American (AMR) AF: 0.560 AC: 8566 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.528 AC: 1828 AN: 3464

East Asian (EAS) AF: 0.590 AC: 3040 AN: 5154

South Asian (SAS) AF: 0.650 AC: 3130 AN: 4818

European-Finnish (FIN) AF: 0.453 AC: 4791 AN: 10568

Middle Eastern (MID) AF: 0.586 AC: 171 AN: 292

European-Non Finnish (NFE) AF: 0.457 AC: 31055 AN: 67982

Other (OTH) AF: 0.552 AC: 1162 AN: 2106

Alfa AF: 0.492 Hom.: 67771

Bravo AF: 0.578

Asia WGS AF: 0.628 AC: 2187 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.9
DANN	Benign	0.61
PhyloP100		-0.97
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: rs11080344; hg19: chr17-26104511;