Variant 7-74779274-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_000265.7(NCF1):c.247G>A(p.Gly83Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0113 in 1,609,980 control chromosomes in the GnomAD database, including 150 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0086 ( 3 hom., cov: 23)

Exomes 𝑓: 0.012 ( 147 hom. )

Consequence

NCF1
NM_000265.7 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.09

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011861771).

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCF1	NM_000265.7 linkuse as main transcript	c.247G>A	p.Gly83Arg	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.247G>A	p.Gly83Arg	missense_variant	4/11	1	NM_000265.7	ENSP00000289473.4		P14598-1

Frequencies

GnomAD3 genomes

AF:

0.00863

AC:

1303

AN:

150984

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00251

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00774

Gnomad ASJ

AF:

0.0107

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000851

Gnomad FIN

AF:

0.0104

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0134

Gnomad OTH

AF:

0.00965

GnomAD3 exomes

AF:

0.00880

AC:

2186

AN:

248444

Hom.:

AF XY:

0.00874

AC XY:

1179

AN XY:

134970

show subpopulations

Gnomad AFR exome

AF:

0.00280

Gnomad AMR exome

AF:

0.00547

Gnomad ASJ exome

AF:

0.00801

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00308

Gnomad FIN exome

AF:

0.0104

Gnomad NFE exome

AF:

0.0134

Gnomad OTH exome

AF:

0.00871

GnomAD4 exome

AF:

0.0116

AC:

16861

AN:

1458878

Hom.:

147

Cov.:

AF XY:

0.0112

AC XY:

8156

AN XY:

725756

show subpopulations

Gnomad4 AFR exome

AF:

0.00251

Gnomad4 AMR exome

AF:

0.00640

Gnomad4 ASJ exome

AF:

0.00834

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00321

Gnomad4 FIN exome

AF:

0.0105

Gnomad4 NFE exome

AF:

0.0133

Gnomad4 OTH exome

AF:

0.0108

GnomAD4 genome

AF:

0.00862

AC:

1302

AN:

151102

Hom.:

Cov.:

AF XY:

0.00823

AC XY:

607

AN XY:

73748

show subpopulations

Gnomad4 AFR

AF:

0.00250

Gnomad4 AMR

AF:

0.00773

Gnomad4 ASJ

AF:

0.0107

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000851

Gnomad4 FIN

AF:

0.0104

Gnomad4 NFE

AF:

0.0134

Gnomad4 OTH

AF:

0.00955

Alfa

AF:

0.0111

Hom.:

ESP6500AA

AF:

0.00251

AC:

ESP6500EA

AF:

0.0118

AC:

101

ExAC

AF:

0.00878

AC:

1065

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2024

NCF1: PP2, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.37

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.21

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.066

Eigen

Benign

0.027

Eigen_PC

Benign

0.035

FATHMM_MKL

Uncertain

0.83

LIST_S2

Uncertain

0.93

MetaRNN

Benign

0.012

MetaSVM

Benign

-0.83

MutationAssessor

Benign

0.94

PrimateAI

Uncertain

0.60

PROVEAN

Benign

0.33

REVEL

Uncertain

0.35

Sift

Benign

0.28

Sift4G

Benign

0.17

Polyphen

1.0

Vest4

0.44

MutPred

0.51

Gain of loop (P = 0.0435);

MVP

0.81

ClinPred

0.026

GERP RS

3.4

Varity_R

0.76

gMVP

0.41

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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