chr17-27772145-T-G

Variant names:

• chr17-27772145-T-G
• rs2274894
• NM_000625.4:c.1704+163A>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.1704+163A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.681 in 152,132 control chromosomes in the GnomAD database, including 35,922 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 0.68 (35922 hom., cov: 33)
• Consequence: NOS2 NM_000625.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.148
• Publications: 24 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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.798 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOS2	NM_000625.4	c.1704+163A>C		intron_variant	Intron 14 of 26	ENST00000313735.11	NP_000616.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOS2	ENST00000313735.11	c.1704+163A>C		intron_variant	Intron 14 of 26	1	NM_000625.4	ENSP00000327251.6

Frequencies

GnomAD3 genomes AF: 0.681 AC: 103489 AN: 152014 Hom.: 35866 Cov.: 33

Gnomad AFR AF: 0.805

Gnomad AMI AF: 0.763

Gnomad AMR AF: 0.659

Gnomad ASJ AF: 0.698

Gnomad EAS AF: 0.683

Gnomad SAS AF: 0.815

Gnomad FIN AF: 0.607

Gnomad MID AF: 0.807

Gnomad NFE AF: 0.609

Gnomad OTH AF: 0.685

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

GnomAD4 genome AF: 0.681 AC: 103608 AN: 152132 Hom.: 35922 Cov.: 33 AF XY: 0.684 AC XY: 50886 AN XY: 74364

African (AFR) AF: 0.805 AC: 33415 AN: 41498

American (AMR) AF: 0.660 AC: 10089 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.698 AC: 2421 AN: 3470

East Asian (EAS) AF: 0.683 AC: 3524 AN: 5158

South Asian (SAS) AF: 0.817 AC: 3933 AN: 4816

European-Finnish (FIN) AF: 0.607 AC: 6419 AN: 10582

Middle Eastern (MID) AF: 0.816 AC: 240 AN: 294

European-Non Finnish (NFE) AF: 0.609 AC: 41422 AN: 68000

Other (OTH) AF: 0.687 AC: 1449 AN: 2110

Alfa AF: 0.632 Hom.: 15705

Bravo AF: 0.684

Asia WGS AF: 0.769 AC: 2676 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.4
DANN	Benign	0.55
PhyloP100		0.15
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: rs2274894; hg19: chr17-26099171;