1-183580622-G-T

Variant names:

• chr1-183580622-G-T
• rs10911363
• NM_000433.4:c.258-2915C>A

Variant summary

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

The NM_000433.4(NCF2):​c.258-2915C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 151,918 control chromosomes in the GnomAD database, including 7,217 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 0.30 (7217 hom., cov: 31)
• Consequence: NCF2 NM_000433.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.140
• Publications: 39 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.53 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000433.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCF2	NM_000433.4	MANE Select	c.258-2915C>A		intron	N/A	NP_000424.2	P19878-1
	NCF2	NM_001127651.3		c.258-2915C>A		intron	N/A	NP_001121123.1	P19878-1
	NCF2	NM_001410895.1		c.258-2915C>A		intron	N/A	NP_001397824.1	A0A8V8TMB9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCF2	ENST00000367535.8	TSL:1 MANE Select	c.258-2915C>A		intron	N/A	ENSP00000356505.4	P19878-1
	NCF2	ENST00000367536.5	TSL:1	c.258-2915C>A		intron	N/A	ENSP00000356506.1	P19878-1
	NCF2	ENST00000946295.1		c.258-2915C>A		intron	N/A	ENSP00000616354.1

Frequencies

GnomAD3 genomes AF: 0.304 AC: 46128 AN: 151798 Hom.: 7209 Cov.: 31

Gnomad AFR AF: 0.311

Gnomad AMI AF: 0.363

Gnomad AMR AF: 0.336

Gnomad ASJ AF: 0.268

Gnomad EAS AF: 0.547

Gnomad SAS AF: 0.377

Gnomad FIN AF: 0.254

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.278

Gnomad OTH AF: 0.304

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

GnomAD4 genome AF: 0.304 AC: 46158 AN: 151918 Hom.: 7217 Cov.: 31 AF XY: 0.305 AC XY: 22679 AN XY: 74236

African (AFR) AF: 0.310 AC: 12856 AN: 41442

American (AMR) AF: 0.336 AC: 5131 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.268 AC: 929 AN: 3472

East Asian (EAS) AF: 0.547 AC: 2817 AN: 5148

South Asian (SAS) AF: 0.374 AC: 1804 AN: 4818

European-Finnish (FIN) AF: 0.254 AC: 2669 AN: 10528

Middle Eastern (MID) AF: 0.231 AC: 67 AN: 290

European-Non Finnish (NFE) AF: 0.278 AC: 18910 AN: 67942

Other (OTH) AF: 0.307 AC: 644 AN: 2100

Alfa AF: 0.290 Hom.: 12998

Bravo AF: 0.311

Asia WGS AF: 0.485 AC: 1680 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.9
DANN	Benign	0.51
PhyloP100		-0.14
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: rs10911363; hg19: chr1-183549757;