chr1-183555720-C-A

Variant names:

• chr1-183555720-C-A
• rs796860
• NM_000433.4:c.*398G>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000433.4(NCF2):​c.*398G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.9 in 206,112 control chromosomes in the GnomAD database, including 83,646 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.90 (61969 hom., cov: 31)
  • Exomes 𝑓: 0.89 (21677 hom.)
• Consequence: NCF2 NM_000433.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.05
• Publications: 12 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 1-183555720-C-A is Benign according to our data. Variant chr1-183555720-C-A is described in ClinVar as Benign. ClinVar VariationId is 294066.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCF2	NM_000433.4	MANE Select	c.*398G>T		3_prime_UTR	Exon 15 of 15	NP_000424.2	P19878-1
	NCF2	NM_001127651.3		c.*398G>T		3_prime_UTR	Exon 16 of 16	NP_001121123.1	P19878-1
	NCF2	NM_001410895.1		c.*398G>T		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.*398G>T		3_prime_UTR	Exon 15 of 15	ENSP00000356505.4	P19878-1
	NCF2	ENST00000367536.5	TSL:1	c.*398G>T		3_prime_UTR	Exon 16 of 16	ENSP00000356506.1	P19878-1
	NCF2	ENST00000946295.1		c.*398G>T		3_prime_UTR	Exon 16 of 16	ENSP00000616354.1

Frequencies

GnomAD3 genomes AF: 0.902 AC: 137087 AN: 152042 Hom.: 61925 Cov.: 31

Gnomad AFR AF: 0.938

Gnomad AMI AF: 0.908

Gnomad AMR AF: 0.895

Gnomad ASJ AF: 0.780

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.948

Gnomad FIN AF: 0.908

Gnomad MID AF: 0.798

Gnomad NFE AF: 0.877

Gnomad OTH AF: 0.870

GnomAD4 exome AF: 0.895 AC: 48265 AN: 53952 Hom.: 21677 Cov.: 0 AF XY: 0.897 AC XY: 25458 AN XY: 28366

African (AFR) AF: 0.948 AC: 1462 AN: 1542

American (AMR) AF: 0.916 AC: 3469 AN: 3788

Ashkenazi Jewish (ASJ) AF: 0.770 AC: 1042 AN: 1354

East Asian (EAS) AF: 0.992 AC: 3325 AN: 3352

South Asian (SAS) AF: 0.939 AC: 6442 AN: 6860

European-Finnish (FIN) AF: 0.905 AC: 1663 AN: 1838

Middle Eastern (MID) AF: 0.874 AC: 152 AN: 174

European-Non Finnish (NFE) AF: 0.876 AC: 28239 AN: 32226

Other (OTH) AF: 0.877 AC: 2471 AN: 2818

GnomAD4 genome AF: 0.902 AC: 137186 AN: 152160 Hom.: 61969 Cov.: 31 AF XY: 0.904 AC XY: 67221 AN XY: 74392

African (AFR) AF: 0.937 AC: 38917 AN: 41522

American (AMR) AF: 0.895 AC: 13672 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.780 AC: 2704 AN: 3466

East Asian (EAS) AF: 0.998 AC: 5172 AN: 5182

South Asian (SAS) AF: 0.947 AC: 4565 AN: 4818

European-Finnish (FIN) AF: 0.908 AC: 9617 AN: 10590

Middle Eastern (MID) AF: 0.810 AC: 235 AN: 290

European-Non Finnish (NFE) AF: 0.877 AC: 59651 AN: 67992

Other (OTH) AF: 0.866 AC: 1827 AN: 2110

Alfa AF: 0.877 Hom.: 88852

Bravo AF: 0.903

Asia WGS AF: 0.946 AC: 3290 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 2 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.32
DANN	Benign	0.42
PhyloP100		-2.0
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: rs796860; hg19: chr1-183524855;