22-36875760-C-T

Position:

chr22-36875760-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000631.5(NCF4):c.735C>T(p.Tyr245Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0825 in 1,613,996 control chromosomes in the GnomAD database, including 6,913 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1407 hom., cov: 32)

Exomes 𝑓: 0.079 ( 5506 hom. )

Consequence

NCF4
NM_000631.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -2.20

Variant links:

Genes affected

NCF4 (HGNC:7662): (neutrophil cytosolic factor 4) The protein encoded by this gene is a cytosolic regulatory component of the superoxide-producing phagocyte NADPH-oxidase, a multicomponent enzyme system important for host defense. This protein is preferentially expressed in cells of myeloid lineage. It interacts primarily with neutrophil cytosolic factor 2 (NCF2/p67-phox) to form a complex with neutrophil cytosolic factor 1 (NCF1/p47-phox), which further interacts with the small G protein RAC1 and translocates to the membrane upon cell stimulation. This complex then activates flavocytochrome b, the membrane-integrated catalytic core of the enzyme system. The PX domain of this protein can bind phospholipid products of the PI(3) kinase, which suggests its role in PI(3) kinase-mediated signaling events. The phosphorylation of this protein was found to negatively regulate the enzyme activity. Alternatively spliced transcript variants encoding distinct isoforms have been observed. [provided by RefSeq, Jul 2008]

NCF4 links:

NCF4 (HGNC:):

NCF4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 22-36875760-C-T is Benign according to our data. Variant chr22-36875760-C-T is described in ClinVar as [Benign]. Clinvar id is 260307.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-36875760-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-2.2 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.213 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCF4	NM_000631.5 linkuse as main transcript	c.735C>T	p.Tyr245Tyr	synonymous_variant	8/10	ENST00000248899.11	NP_000622.2	Q15080-1
NCF4	NM_013416.4 linkuse as main transcript	c.735C>T	p.Tyr245Tyr	synonymous_variant	8/9		NP_038202.2	Q15080-3
NCF4	XM_047441384.1 linkuse as main transcript	c.909C>T	p.Tyr303Tyr	synonymous_variant	9/11		XP_047297340.1
NCF4	XM_047441385.1 linkuse as main transcript	c.879C>T	p.Tyr293Tyr	synonymous_variant	9/11		XP_047297341.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NCF4	ENST00000248899.11 linkuse as main transcript	c.735C>T	p.Tyr245Tyr	synonymous_variant	8/10	1	NM_000631.5	ENSP00000248899.6		Q15080-1

Frequencies

GnomAD3 genomes

AF:

0.118

AC:

17946

AN:

152064

Hom.:

1405

Cov.:

show subpopulations

Gnomad AFR

AF:

0.217

Gnomad AMI

AF:

0.0429

Gnomad AMR

AF:

0.151

Gnomad ASJ

AF:

0.0922

Gnomad EAS

AF:

0.0538

Gnomad SAS

AF:

0.106

Gnomad FIN

AF:

0.0573

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.0683

Gnomad OTH

AF:

0.114

GnomAD3 exomes

AF:

0.0957

AC:

24056

AN:

251378

Hom.:

1533

AF XY:

0.0921

AC XY:

12516

AN XY:

135878

show subpopulations

Gnomad AFR exome

AF:

0.222

Gnomad AMR exome

AF:

0.175

Gnomad ASJ exome

AF:

0.0875

Gnomad EAS exome

AF:

0.0530

Gnomad SAS exome

AF:

0.106

Gnomad FIN exome

AF:

0.0585

Gnomad NFE exome

AF:

0.0662

Gnomad OTH exome

AF:

0.0807

GnomAD4 exome

AF:

0.0787

AC:

115100

AN:

1461814

Hom.:

5506

Cov.:

AF XY:

0.0790

AC XY:

57464

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.227

Gnomad4 AMR exome

AF:

0.171

Gnomad4 ASJ exome

AF:

0.0852

Gnomad4 EAS exome

AF:

0.0455

Gnomad4 SAS exome

AF:

0.108

Gnomad4 FIN exome

AF:

0.0582

Gnomad4 NFE exome

AF:

0.0696

Gnomad4 OTH exome

AF:

0.0898

GnomAD4 genome

AF:

0.118

AC:

17984

AN:

152182

Hom.:

1407

Cov.:

AF XY:

0.118

AC XY:

8787

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.217

Gnomad4 AMR

AF:

0.151

Gnomad4 ASJ

AF:

0.0922

Gnomad4 EAS

AF:

0.0533

Gnomad4 SAS

AF:

0.107

Gnomad4 FIN

AF:

0.0573

Gnomad4 NFE

AF:

0.0683

Gnomad4 OTH

AF:

0.114

Alfa

AF:

0.0773

Hom.:

1191

Bravo

AF:

0.130

Asia WGS

AF:

0.0840

AC:

294

AN:

3478

EpiCase

AF:

0.0707

EpiControl

AF:

0.0702

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jan 24, 2024	This variant is classified as Benign based on local population frequency. This variant was detected in 21% of patients studied by a panel of primary immunodeficiencies. Number of patients: 20. Only high quality variants are reported. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 28, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: MAF -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 16, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 3

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

0.15

DANN

Benign

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over