rs11588654

Variant names:

• chr1-183587260-T-C
• rs11588654
• NM_000433.4:c.175-283A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000433.4(NCF2):​c.175-283A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 152,122 control chromosomes in the GnomAD database, including 5,433 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.24 (5433 hom., cov: 31)
• Consequence: NCF2 NM_000433.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.10
• Publications: 10 publications found

Genes affected

NCF2 (HGNC:7661): (neutrophil cytosolic factor 2) This gene encodes neutrophil cytosolic factor 2, the 67-kilodalton cytosolic subunit of the multi-protein NADPH oxidase complex found in neutrophils. This oxidase produces a burst of superoxide which is delivered to the lumen of the neutrophil phagosome. Mutations in this gene, as well as in other NADPH oxidase subunits, can result in chronic granulomatous disease, a disease that causes recurrent infections by catalase-positive organisms. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jun 2010]

ENSG00000289732 (HGNC:):

SMG7 (HGNC:16792): (SMG7 nonsense mediated mRNA decay factor) This gene encodes a protein that is essential for nonsense-mediated mRNA decay (NMD); a process whereby transcripts with premature termination codons are targeted for rapid degradation by a mRNA decay complex. The mRNA decay complex consists, in part, of this protein along with proteins SMG5 and UPF1. The N-terminal domain of this protein is thought to mediate its association with SMG5 or UPF1 while the C-terminal domain interacts with the mRNA decay complex. This protein may therefore couple changes in UPF1 phosphorylation state to the degradation of NMD-candidate transcripts. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Aug 2011]

SMG7 Gene-Disease associations (from GenCC):

• autoimmune disease

  Inheritance: AD Classification: NO_KNOWN Submitted by: Illumina

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 1-183587260-T-C is Benign according to our data. Variant chr1-183587260-T-C is described in ClinVar as Benign. ClinVar VariationId is 1261246.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.334 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCF2	NM_000433.4	c.175-283A>G		intron_variant	Intron 1 of 14	ENST00000367535.8	NP_000424.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCF2	ENST00000367535.8	c.175-283A>G		intron_variant	Intron 1 of 14	1	NM_000433.4	ENSP00000356505.4

Frequencies

GnomAD3 genomes AF: 0.245 AC: 37242 AN: 152004 Hom.: 5435 Cov.: 31

Gnomad AFR AF: 0.0838

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.320

Gnomad EAS AF: 0.0905

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.318

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.337

Gnomad OTH AF: 0.261

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

GnomAD4 genome AF: 0.245 AC: 37228 AN: 152122 Hom.: 5433 Cov.: 31 AF XY: 0.244 AC XY: 18145 AN XY: 74348

African (AFR) AF: 0.0835 AC: 3469 AN: 41524

American (AMR) AF: 0.252 AC: 3849 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.320 AC: 1109 AN: 3466

East Asian (EAS) AF: 0.0899 AC: 465 AN: 5170

South Asian (SAS) AF: 0.249 AC: 1204 AN: 4826

European-Finnish (FIN) AF: 0.318 AC: 3357 AN: 10570

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.337 AC: 22925 AN: 67962

Other (OTH) AF: 0.259 AC: 547 AN: 2114

Alfa AF: 0.288 Hom.: 1366

Bravo AF: 0.233

Asia WGS AF: 0.168 AC: 585 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 08, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	1.1
DANN	Benign	0.47
PhyloP100		-1.1
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: rs11588654; hg19: chr1-183556395;