chr1-183555571-A-AAAAC

Variant names:

• chr1-183555571-A-AAAAC
• rs376681445
• NM_000433.4:c.*543_*546dupGTTT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_000433.4(NCF2):​c.*543_*546dupGTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000237 in 152,212 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00024 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NCF2 NM_000433.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.343
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

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.*543_*546dupGTTT		3_prime_UTR	Exon 15 of 15	NP_000424.2	P19878-1
	NCF2	NM_001127651.3		c.*543_*546dupGTTT		3_prime_UTR	Exon 16 of 16	NP_001121123.1	P19878-1
	NCF2	NM_001410895.1		c.*543_*546dupGTTT		3_prime_UTR	Exon 15 of 15	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.*543_*546dupGTTT		3_prime_UTR	Exon 15 of 15	ENSP00000356505.4	P19878-1
	NCF2	ENST00000367536.5	TSL:1	c.*543_*546dupGTTT		3_prime_UTR	Exon 16 of 16	ENSP00000356506.1	P19878-1
	NCF2	ENST00000946293.1		c.*543_*546dupGTTT		splice_region	Exon 12 of 12	ENSP00000616352.1

Frequencies

GnomAD3 genomes AF: 0.000237 AC: 36 AN: 152212 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000426

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 4152 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2156

African (AFR) AF: 0.00 AC: 0 AN: 14

American (AMR) AF: 0.00 AC: 0 AN: 960

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10

East Asian (EAS) AF: 0.00 AC: 0 AN: 244

South Asian (SAS) AF: 0.00 AC: 0 AN: 434

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 24

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2346

Other (OTH) AF: 0.00 AC: 0 AN: 116

GnomAD4 genome AF: 0.000237 AC: 36 AN: 152212 Hom.: 0 Cov.: 32 AF XY: 0.000296 AC XY: 22 AN XY: 74376

African (AFR) AF: 0.000145 AC: 6 AN: 41456

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000426 AC: 29 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000542 Hom.: 0

Bravo AF: 0.000181

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.34

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs376681445; hg19: chr1-183524706;