Variant rs371707791 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_000397.4(CYBB):c.1462-7C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000168 in 1,193,617 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000090 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 9.2e-7 ( 0 hom. 1 hem. )

Consequence

CYBB
NM_000397.4 splice_region, intron

Scores

Splicing: ADA: 0.0005734

Clinical Significance

Likely benign criteria provided, single submitter U:1B:1

Conservation

PhyloP100: -0.192

Variant links:

Genes affected

CYBB (HGNC:2578): (cytochrome b-245 beta chain) Cytochrome b (-245) is composed of cytochrome b alpha (CYBA) and beta (CYBB) chain. It has been proposed as a primary component of the microbicidal oxidase system of phagocytes. CYBB deficiency is one of five described biochemical defects associated with chronic granulomatous disease (CGD). In this disorder, there is decreased activity of phagocyte NADPH oxidase; neutrophils are able to phagocytize bacteria but cannot kill them in the phagocytic vacuoles. The cause of the killing defect is an inability to increase the cell's respiration and consequent failure to deliver activated oxygen into the phagocytic vacuole. [provided by RefSeq, Jul 2008]

CYBB links:

ENSG00000250349 (HGNC:):

ENSG00000250349 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant X-37809560-C-A is Benign according to our data. Variant chrX-37809560-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 533557.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYBB	NM_000397.4 linkuse as main transcript	c.1462-7C>A		splice_region_variant, intron_variant		ENST00000378588.5	NP_000388.2	P04839A0A0S2Z3S6
CYBB	XM_047441855.1 linkuse as main transcript	c.1156-7C>A		splice_region_variant, intron_variant			XP_047297811.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
CYBB	ENST00000378588.5 linkuse as main transcript	c.1462-7C>A	splice_region_variant, intron_variant	1	NM_000397.4	ENSP00000367851.4	P04839
ENSG00000250349	ENST00000465127.1 linkuse as main transcript	c.171+383560C>A	intron_variant	5		ENSP00000417050.1	B4E171
CYBB	ENST00000696171.1 linkuse as main transcript	c.1366-7C>A	splice_region_variant, intron_variant			ENSP00000512462.1	A0A8Q3SIJ1
CYBB	ENST00000696170.1 linkuse as main transcript	n.*971-7C>A	splice_region_variant, intron_variant			ENSP00000512461.1	A0A8Q3WMA3

Frequencies

GnomAD3 genomes

AF:

0.00000901

AC:

AN:

110966

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33216

show subpopulations

Gnomad AFR

AF:

0.0000328

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000128

AC:

AN:

155966

Hom.:

AF XY:

0.00

AC XY:

AN XY:

48190

show subpopulations

Gnomad AFR exome

AF:

0.000172

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

9.24e-7

AC:

AN:

1082651

Hom.:

Cov.:

AF XY:

0.00000283

AC XY:

AN XY:

353107

show subpopulations

Gnomad4 AFR exome

AF:

0.0000382

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000901

AC:

AN:

110966

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33216

show subpopulations

Gnomad4 AFR

AF:

0.0000328

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ClinVar

Significance: Likely benign

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Chronic granulomatous disease

Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

Natera, Inc.

Oct 20, 2020

- -

Granulomatous disease, chronic, X-linked

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 04, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

6.4

DANN

Benign

0.58

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00057

dbscSNV1_RF

Benign

0.080

SpliceAI score (max)

0.17

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