Variant 7-74777383-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000265.7(NCF1):c.153+36C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0153 in 1,457,970 control chromosomes in the GnomAD database, including 131 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 9 hom., cov: 21)

Exomes 𝑓: 0.016 ( 122 hom. )

Consequence

NCF1
NM_000265.7 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.651

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 7-74777383-C-T is Benign according to our data. Variant chr7-74777383-C-T is described in ClinVar as [Benign]. Clinvar id is 1231830.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0125 (1792/143376) while in subpopulation NFE AF= 0.0188 (1238/65766). AF 95% confidence interval is 0.018. There are 9 homozygotes in gnomad4. There are 847 alleles in male gnomad4 subpopulation. Median coverage is 21. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCF1	NM_000265.7 linkuse as main transcript	c.153+36C>T		intron_variant		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.153+36C>T		intron_variant		1	NM_000265.7	ENSP00000289473.4		P14598-1

Frequencies

GnomAD3 genomes

AF:

0.0125

AC:

1790

AN:

143260

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00347

Gnomad AMI

AF:

0.00339

Gnomad AMR

AF:

0.0145

Gnomad ASJ

AF:

0.0170

Gnomad EAS

AF:

0.000455

Gnomad SAS

AF:

0.00822

Gnomad FIN

AF:

0.00892

Gnomad MID

AF:

0.0197

Gnomad NFE

AF:

0.0188

Gnomad OTH

AF:

0.0120

GnomAD3 exomes

AF:

0.0139

AC:

3062

AN:

221072

Hom.:

AF XY:

0.0140

AC XY:

1674

AN XY:

119276

show subpopulations

Gnomad AFR exome

AF:

0.00375

Gnomad AMR exome

AF:

0.0118

Gnomad ASJ exome

AF:

0.0179

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00935

Gnomad FIN exome

AF:

0.00780

Gnomad NFE exome

AF:

0.0199

Gnomad OTH exome

AF:

0.0147

GnomAD4 exome

AF:

0.0157

AC:

20577

AN:

1314594

Hom.:

122

Cov.:

AF XY:

0.0155

AC XY:

10197

AN XY:

657152

show subpopulations

Gnomad4 AFR exome

AF:

0.00286

Gnomad4 AMR exome

AF:

0.0101

Gnomad4 ASJ exome

AF:

0.0159

Gnomad4 EAS exome

AF:

0.0000598

Gnomad4 SAS exome

AF:

0.00779

Gnomad4 FIN exome

AF:

0.00613

Gnomad4 NFE exome

AF:

0.0178

Gnomad4 OTH exome

AF:

0.0158

GnomAD4 genome

AF:

0.0125

AC:

1792

AN:

143376

Hom.:

Cov.:

AF XY:

0.0122

AC XY:

847

AN XY:

69494

show subpopulations

Gnomad4 AFR

AF:

0.00346

Gnomad4 AMR

AF:

0.0145

Gnomad4 ASJ

AF:

0.0170

Gnomad4 EAS

AF:

0.000456

Gnomad4 SAS

AF:

0.00845

Gnomad4 FIN

AF:

0.00892

Gnomad4 NFE

AF:

0.0188

Gnomad4 OTH

AF:

0.0118

Alfa

AF:

0.0141

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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	Mar 03, 2015	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

4.5

DANN

Benign

0.75

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