Variant 7-74779319-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6BS2

The NM_000265.7(NCF1):c.292T>G(p.Cys98Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00131 in 1,608,052 control chromosomes in the GnomAD database, including 39 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0012 ( 4 hom., cov: 23)

Exomes 𝑓: 0.0013 ( 35 hom. )

Consequence

NCF1
NM_000265.7 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:4B:1

Conservation

PhyloP100: 5.54

Variant links:

Genes affected

NCF1 (HGNC:7660): (neutrophil cytosolic factor 1) The protein encoded by this gene is a 47 kDa cytosolic subunit of neutrophil NADPH oxidase. This oxidase is a multicomponent enzyme that is activated to produce superoxide anion. Mutations in this gene have been associated with chronic granulomatous disease. [provided by RefSeq, Jul 2008]

NCF1 links:

NCF1 (HGNC:):

NCF1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP6

Variant 7-74779319-T-G is Benign according to our data. Variant chr7-74779319-T-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 1175021.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}. Variant chr7-74779319-T-G is described in Lovd as [Benign].

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCF1	NM_000265.7 linkuse as main transcript	c.292T>G	p.Cys98Gly	missense_variant	4/11	ENST00000289473.11	NP_000256.4	P14598-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NCF1	ENST00000289473.11 linkuse as main transcript	c.292T>G	p.Cys98Gly	missense_variant	4/11	1	NM_000265.7	ENSP00000289473.4		P14598-1

Frequencies

GnomAD3 genomes

AF:

0.00117

AC:

174

AN:

148878

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000275

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000536

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000871

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00212

Gnomad OTH

AF:

0.00146

GnomAD3 exomes

AF:

0.000830

AC:

185

AN:

222758

Hom.:

AF XY:

0.000749

AC XY:

AN XY:

120238

show subpopulations

Gnomad AFR exome

AF:

0.0000686

Gnomad AMR exome

AF:

0.000725

Gnomad ASJ exome

AF:

0.000532

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000710

Gnomad NFE exome

AF:

0.00142

Gnomad OTH exome

AF:

0.000716

GnomAD4 exome

AF:

0.00132

AC:

1928

AN:

1459054

Hom.:

Cov.:

AF XY:

0.00130

AC XY:

940

AN XY:

725792

show subpopulations

Gnomad4 AFR exome

AF:

0.0000899

Gnomad4 AMR exome

AF:

0.00123

Gnomad4 ASJ exome

AF:

0.000536

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00104

Gnomad4 NFE exome

AF:

0.00155

Gnomad4 OTH exome

AF:

0.00138

GnomAD4 genome

AF:

0.00117

AC:

174

AN:

148998

Hom.:

Cov.:

AF XY:

0.000868

AC XY:

AN XY:

72608

show subpopulations

Gnomad4 AFR

AF:

0.000274

Gnomad4 AMR

AF:

0.000536

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000871

Gnomad4 NFE

AF:

0.00212

Gnomad4 OTH

AF:

0.00145

Alfa

AF:

0.00123

Hom.:

Bravo

AF:

0.00104

ESP6500AA

AF:

0.000234

AC:

ESP6500EA

AF:

0.000722

AC:

ExAC

AF:

0.000690

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:4Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:3Benign:1

Uncertain significance, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2023	NCF1: PP2, BS2 -
Uncertain significance, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Uncertain significance, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 1

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

May 13, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.12

CADD

Uncertain

DANN

Benign

0.76

DEOGEN2

Uncertain

0.49

Eigen

Uncertain

0.26

Eigen_PC

Benign

0.055

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.84

M_CAP

Uncertain

0.21

MetaRNN

Uncertain

0.51

MetaSVM

Benign

-0.54

MutationAssessor

Pathogenic

3.4

PrimateAI

Uncertain

0.67

PROVEAN

Pathogenic

-9.8

REVEL

Benign

0.23

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.025

Polyphen

0.76

Vest4

0.69

MVP

0.78

ClinPred

0.20

GERP RS

2.0

Varity_R

0.87

gMVP

0.65

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

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