chr17-27764201-C-T

Variant names:

• chr17-27764201-C-T
• rs2297511
• NM_000625.4:c.2429-57G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_000625.4(NOS2):​c.2429-57G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.523 in 915,438 control chromosomes in the GnomAD database, including 134,255 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 0.67 (33358 hom., cov: 23)
  • Exomes 𝑓: 0.50 (100897 hom.)
• Consequence: NOS2 NM_000625.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.441
• 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BS2: High Homozygotes in GnomAd4 at 33358 Unknown gene

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.2429-57G>A		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.2429-57G>A		intron	N/A	ENSP00000327251.6
	NOS2	ENST00000646938.1		c.2426-57G>A		intron	N/A	ENSP00000494870.1
	NOS2	ENST00000697339.1		c.1391-57G>A		intron	N/A	ENSP00000513261.1

Frequencies

GnomAD3 genomes AF: 0.668 AC: 97977 AN: 146696 Hom.: 33303 Cov.: 23

Gnomad AFR AF: 0.767

Gnomad AMI AF: 0.761

Gnomad AMR AF: 0.658

Gnomad ASJ AF: 0.684

Gnomad EAS AF: 0.682

Gnomad SAS AF: 0.826

Gnomad FIN AF: 0.583

Gnomad MID AF: 0.799

Gnomad NFE AF: 0.609

Gnomad OTH AF: 0.680

GnomAD4 exome AF: 0.495 AC: 380634 AN: 768622 Hom.: 100897 AF XY: 0.510 AC XY: 195820 AN XY: 384218

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.674 AC: 8673 AN: 12876

American (AMR) AF: 0.527 AC: 8180 AN: 15514

Ashkenazi Jewish (ASJ) AF: 0.636 AC: 9066 AN: 14258

East Asian (EAS) AF: 0.707 AC: 18234 AN: 25794

South Asian (SAS) AF: 0.782 AC: 33597 AN: 42954

European-Finnish (FIN) AF: 0.565 AC: 23585 AN: 41752

Middle Eastern (MID) AF: 0.699 AC: 1617 AN: 2312

European-Non Finnish (NFE) AF: 0.447 AC: 259015 AN: 579218

Other (OTH) AF: 0.550 AC: 18667 AN: 33944

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.668 AC: 98094 AN: 146816 Hom.: 33358 Cov.: 23 AF XY: 0.670 AC XY: 47792 AN XY: 71362

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.768 AC: 30355 AN: 39546

American (AMR) AF: 0.658 AC: 9724 AN: 14768

Ashkenazi Jewish (ASJ) AF: 0.684 AC: 2339 AN: 3418

East Asian (EAS) AF: 0.681 AC: 3307 AN: 4854

South Asian (SAS) AF: 0.828 AC: 3651 AN: 4412

European-Finnish (FIN) AF: 0.583 AC: 5930 AN: 10166

Middle Eastern (MID) AF: 0.809 AC: 233 AN: 288

European-Non Finnish (NFE) AF: 0.609 AC: 40512 AN: 66472

Other (OTH) AF: 0.682 AC: 1366 AN: 2002

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.640 Hom.: 3372

Bravo AF: 0.675

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.41
DANN	Benign	0.38
PhyloP100		-0.44
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: rs2297511; hg19: chr17-26091227;