chr1-183556317-T-A

Variant names:

• chr1-183556317-T-A
• rs699244
• NM_000433.4:c.1469-87A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000433.4(NCF2):​c.1469-87A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00202 in 1,218,508 control chromosomes in the GnomAD database, including 33 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 0.0094 (18 hom., cov: 31)
  • Exomes 𝑓: 0.00096 (15 hom.)
• Consequence: NCF2 NM_000433.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.384
• Publications: 8 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=-0.92).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00943 (1436/152228) while in subpopulation AFR AF = 0.0329 (1365/41524). AF 95% confidence interval is 0.0314. There are 18 homozygotes in GnomAd4. There are 669 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 18 AR gene

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.1469-87A>T		intron	N/A	NP_000424.2	P19878-1
	NCF2	NM_001127651.3		c.1469-87A>T		intron	N/A	NP_001121123.1	P19878-1
	NCF2	NM_001410895.1		c.1361-87A>T		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.1469-87A>T		intron	N/A	ENSP00000356505.4	P19878-1
	NCF2	ENST00000367536.5	TSL:1	c.1469-87A>T		intron	N/A	ENSP00000356506.1	P19878-1
	NCF2	ENST00000946295.1		c.1664-87A>T		intron	N/A	ENSP00000616354.1

Frequencies

GnomAD3 genomes AF: 0.00941 AC: 1431 AN: 152110 Hom.: 18 Cov.: 31

Gnomad AFR AF: 0.0328

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00334

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00813

GnomAD4 exome AF: 0.000960 AC: 1024 AN: 1066280 Hom.: 15 AF XY: 0.000783 AC XY: 428 AN XY: 546720

African (AFR) AF: 0.0315 AC: 812 AN: 25792

American (AMR) AF: 0.00168 AC: 71 AN: 42162

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23482

East Asian (EAS) AF: 0.0000266 AC: 1 AN: 37656

South Asian (SAS) AF: 0.0000260 AC: 2 AN: 77020

European-Finnish (FIN) AF: 0.0000195 AC: 1 AN: 51176

Middle Eastern (MID) AF: 0.000993 AC: 5 AN: 5034

European-Non Finnish (NFE) AF: 0.0000278 AC: 21 AN: 756672

Other (OTH) AF: 0.00235 AC: 111 AN: 47286

GnomAD4 genome AF: 0.00943 AC: 1436 AN: 152228 Hom.: 18 Cov.: 31 AF XY: 0.00899 AC XY: 669 AN XY: 74430

African (AFR) AF: 0.0329 AC: 1365 AN: 41524

American (AMR) AF: 0.00333 AC: 51 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68014

Other (OTH) AF: 0.00804 AC: 17 AN: 2114

Alfa AF: 0.00 Hom.: 4649

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.88
DANN	Benign	0.19
PhyloP100		0.38
Mutation Taster		=100/0	polymorphism

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: rs699244; hg19: chr1-183525452;