rs789181

Variant names:

• chr1-183557203-G-A
• rs789181
• NM_000433.4:c.1469-973C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-183557203-G-A
• chr1-183557203-G-C
• chr1-183557203-G-T

Variant summary

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

The NM_000433.4(NCF2):​c.1469-973C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.901 in 152,258 control chromosomes in the GnomAD database, including 61,979 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 0.90 (61979 hom., cov: 32)
• Consequence: NCF2 NM_000433.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.535
• Publications: 6 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCF2	NM_000433.4	MANE Select	c.1469-973C>T		intron	N/A	NP_000424.2
	NCF2	NM_001127651.3		c.1469-973C>T		intron	N/A	NP_001121123.1
	NCF2	NM_001410895.1		c.1361-973C>T		intron	N/A	NP_001397824.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCF2	ENST00000367535.8	TSL:1 MANE Select	c.1469-973C>T		intron	N/A	ENSP00000356505.4
	NCF2	ENST00000367536.5	TSL:1	c.1469-973C>T		intron	N/A	ENSP00000356506.1
	NCF2	ENST00000946295.1		c.1663+20C>T		intron	N/A	ENSP00000616354.1

Frequencies

GnomAD3 genomes AF: 0.901 AC: 137142 AN: 152140 Hom.: 61935 Cov.: 32

Gnomad AFR AF: 0.937

Gnomad AMI AF: 0.908

Gnomad AMR AF: 0.894

Gnomad ASJ AF: 0.780

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.947

Gnomad FIN AF: 0.908

Gnomad MID AF: 0.799

Gnomad NFE AF: 0.877

Gnomad OTH AF: 0.871

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

GnomAD4 genome AF: 0.901 AC: 137241 AN: 152258 Hom.: 61979 Cov.: 32 AF XY: 0.903 AC XY: 67245 AN XY: 74446

African (AFR) AF: 0.937 AC: 38935 AN: 41554

American (AMR) AF: 0.894 AC: 13671 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.780 AC: 2707 AN: 3472

East Asian (EAS) AF: 0.998 AC: 5173 AN: 5184

South Asian (SAS) AF: 0.947 AC: 4574 AN: 4828

European-Finnish (FIN) AF: 0.908 AC: 9619 AN: 10596

Middle Eastern (MID) AF: 0.812 AC: 237 AN: 292

European-Non Finnish (NFE) AF: 0.877 AC: 59670 AN: 68026

Other (OTH) AF: 0.867 AC: 1827 AN: 2108

Alfa AF: 0.898 Hom.: 12385

Bravo AF: 0.902

Asia WGS AF: 0.946 AC: 3289 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.9
DANN	Benign	0.71
PhyloP100		-0.54
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs789181; hg19: chr1-183526338;