rs36113295

Variant names:

• chr1-183564040-A-C
• rs36113295
• NM_000433.4:c.1001-10T>G

Your query was ambiguous. Multiple possible variants found:

• chr1-183564040-A-C
• chr1-183564040-A-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_000433.4(NCF2):​c.1001-10T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0168 in 1,608,752 control chromosomes in the GnomAD database, including 307 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.012 (24 hom., cov: 32)
  • Exomes 𝑓: 0.017 (283 hom.)
• Consequence: NCF2 NM_000433.4 intron
• Scores: Splicing: ADA: 0.004408
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 1.10

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=-0.55).
• BP6: Variant 1-183564040-A-C is Benign according to our data. Variant chr1-183564040-A-C is described in ClinVar as [Benign]. Clinvar id is 256114.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-183564040-A-C is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0122 (1851/152304) while in subpopulation NFE AF= 0.022 (1497/68030). AF 95% confidence interval is 0.0211. There are 24 homozygotes in gnomad4. There are 807 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 24 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCF2	NM_000433.4	c.1001-10T>G		intron_variant	Intron 10 of 14	ENST00000367535.8	NP_000424.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCF2	ENST00000367535.8	c.1001-10T>G		intron_variant	Intron 10 of 14	1	NM_000433.4	ENSP00000356505.4

Frequencies

GnomAD3 genomes AF: 0.0122 AC: 1850 AN: 152186 Hom.: 24 Cov.: 32

Gnomad AFR AF: 0.00292

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.00563

Gnomad ASJ AF: 0.00663

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00435

Gnomad FIN AF: 0.00688

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0220

Gnomad OTH AF: 0.00716

GnomAD3 exomes AF: 0.0121 AC: 3047 AN: 251434 Hom.: 32 AF XY: 0.0122 AC XY: 1661 AN XY: 135888

Gnomad AFR exome AF: 0.00258

Gnomad AMR exome AF: 0.00286

Gnomad ASJ exome AF: 0.00556

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00444

Gnomad FIN exome AF: 0.00873

Gnomad NFE exome AF: 0.0215

Gnomad OTH exome AF: 0.0138

GnomAD4 exome AF: 0.0173 AC: 25186 AN: 1456448 Hom.: 283 Cov.: 31 AF XY: 0.0171 AC XY: 12419 AN XY: 724986

Gnomad4 AFR exome AF: 0.00267

Gnomad4 AMR exome AF: 0.00335

Gnomad4 ASJ exome AF: 0.00532

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.00460

Gnomad4 FIN exome AF: 0.00962

Gnomad4 NFE exome AF: 0.0208

Gnomad4 OTH exome AF: 0.0122

GnomAD4 genome AF: 0.0122 AC: 1851 AN: 152304 Hom.: 24 Cov.: 32 AF XY: 0.0108 AC XY: 807 AN XY: 74476

Gnomad4 AFR AF: 0.00291

Gnomad4 AMR AF: 0.00562

Gnomad4 ASJ AF: 0.00663

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00435

Gnomad4 FIN AF: 0.00688

Gnomad4 NFE AF: 0.0220

Gnomad4 OTH AF: 0.00709

Alfa AF: 0.0172 Hom.: 8

Bravo AF: 0.0113

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Apr 03, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 2 Benign:2

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	17
DANN	Benign	0.91

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0044
dbscSNV1_RF	Benign	0.13
SpliceAI score (max)		0.060		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: rs36113295; hg19: chr1-183533175;