rs10797888

Positions:

• chr1-183577897-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000433.4(NCF2):​c.258-190A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0889 in 152,134 control chromosomes in the GnomAD database, including 741 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.089 (741 hom., cov: 32)
• Consequence: NCF2 NM_000433.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.884

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 1-183577897-T-C is Benign according to our data. Variant chr1-183577897-T-C is described in ClinVar as [Benign]. Clinvar id is 1287669.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCF2	NM_000433.4	c.258-190A>G		intron_variant		ENST00000367535.8	NP_000424.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NCF2	ENST00000367535.8	c.258-190A>G		intron_variant		1	NM_000433.4	ENSP00000356505	P1

Frequencies

GnomAD3 genomes AF: 0.0889 AC: 13518 AN: 152016 Hom.: 741 Cov.: 32

Gnomad AFR AF: 0.0238

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.0795

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.0835

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

GnomAD4 genome AF: 0.0889 AC: 13525 AN: 152134 Hom.: 741 Cov.: 32 AF XY: 0.0902 AC XY: 6709 AN XY: 74370

Gnomad4 AFR AF: 0.0238

Gnomad4 AMR AF: 0.144

Gnomad4 ASJ AF: 0.0795

Gnomad4 EAS AF: 0.105

Gnomad4 SAS AF: 0.104

Gnomad4 FIN AF: 0.111

Gnomad4 NFE AF: 0.111

Gnomad4 OTH AF: 0.0826

Alfa AF: 0.102 Hom.: 107

Bravo AF: 0.0886

Asia WGS AF: 0.0860 AC: 300 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 04, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.17
DANN	Benign	0.33

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

Publications

LitVar

Other links and lift over

dbSNP: rs10797888; hg19: chr1-183547032;