1-183565409-C-G

Variant names:

• chr1-183565409-C-G
• rs4652813
• NM_000433.4:c.1000+295G>C

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.1000+295G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.874 in 152,240 control chromosomes in the GnomAD database, including 58,256 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.87 (58256 hom., cov: 31)
• Consequence: NCF2 NM_000433.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.390
• 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]

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=-0.9).
• BP6: Variant 1-183565409-C-G is Benign according to our data. Variant chr1-183565409-C-G is described in ClinVar as Benign. ClinVar VariationId is 1282868.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCF2	NM_000433.4	c.1000+295G>C		intron_variant	Intron 10 of 14	ENST00000367535.8	NP_000424.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCF2	ENST00000367535.8	c.1000+295G>C		intron_variant	Intron 10 of 14	1	NM_000433.4	ENSP00000356505.4

Frequencies

GnomAD3 genomes AF: 0.874 AC: 132902 AN: 152122 Hom.: 58210 Cov.: 31

Gnomad AFR AF: 0.838

Gnomad AMI AF: 0.908

Gnomad AMR AF: 0.889

Gnomad ASJ AF: 0.780

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.947

Gnomad FIN AF: 0.908

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.877

Gnomad OTH AF: 0.852

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

GnomAD4 genome AF: 0.874 AC: 132999 AN: 152240 Hom.: 58256 Cov.: 31 AF XY: 0.876 AC XY: 65185 AN XY: 74438

African (AFR) AF: 0.838 AC: 34798 AN: 41520

American (AMR) AF: 0.889 AC: 13592 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.780 AC: 2708 AN: 3470

East Asian (EAS) AF: 0.998 AC: 5174 AN: 5184

South Asian (SAS) AF: 0.947 AC: 4571 AN: 4828

European-Finnish (FIN) AF: 0.908 AC: 9629 AN: 10608

Middle Eastern (MID) AF: 0.813 AC: 239 AN: 294

European-Non Finnish (NFE) AF: 0.877 AC: 59667 AN: 68022

Other (OTH) AF: 0.848 AC: 1793 AN: 2114

Alfa AF: 0.875 Hom.: 6820

Bravo AF: 0.872

Asia WGS AF: 0.941 AC: 3274 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	-0.90
CADD	Benign	1.0
DANN	Benign	0.36
PhyloP100		-0.39
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: rs4652813; hg19: chr1-183534544;