X-37805187-C-T

Position:

• chrX-37805187-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000397.4(CYBB):​c.1314+19C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00812 in 1,203,163 control chromosomes in the GnomAD database, including 466 homozygotes. There are 2,592 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.041 (233 hom., 1232 hem., cov: 23)
  • Exomes 𝑓: 0.0047 (233 hom. 1360 hem.)
• Consequence: CYBB NM_000397.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.678

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]

ENSG00000250349 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant X-37805187-C-T is Benign according to our data. Variant chrX-37805187-C-T is described in ClinVar as [Benign]. Clinvar id is 35968.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.137 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYBB	NM_000397.4	c.1314+19C>T		intron_variant		ENST00000378588.5	NP_000388.2
CYBB	XM_047441855.1	c.1008+19C>T		intron_variant			XP_047297811.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYBB	ENST00000378588.5	c.1314+19C>T		intron_variant		1	NM_000397.4	ENSP00000367851.4
ENSG00000250349	ENST00000465127.1	c.171+379187C>T		intron_variant		5		ENSP00000417050.1
CYBB	ENST00000696171.1	c.1218+19C>T		intron_variant				ENSP00000512462.1
CYBB	ENST00000696170.1	n.*823+19C>T		intron_variant				ENSP00000512461.1

Frequencies

GnomAD3 genomes AF: 0.0410 AC: 4594 AN: 112010 Hom.: 233 Cov.: 23 AF XY: 0.0357 AC XY: 1221 AN XY: 34224

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0191

Gnomad ASJ AF: 0.000378

Gnomad EAS AF: 0.000281

Gnomad SAS AF: 0.000737

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0169

Gnomad NFE AF: 0.000676

Gnomad OTH AF: 0.0318

GnomAD3 exomes AF: 0.0119 AC: 2146 AN: 179935 Hom.: 100 AF XY: 0.00767 AC XY: 499 AN XY: 65093

Gnomad AFR exome AF: 0.141

Gnomad AMR exome AF: 0.00823

Gnomad ASJ exome AF: 0.000537

Gnomad EAS exome AF: 0.000362

Gnomad SAS exome AF: 0.000213

Gnomad FIN exome AF: 0.0000672

Gnomad NFE exome AF: 0.000511

Gnomad OTH exome AF: 0.00493

GnomAD4 exome AF: 0.00474 AC: 5170 AN: 1091099 Hom.: 233 Cov.: 30 AF XY: 0.00381 AC XY: 1360 AN XY: 357127

Gnomad4 AFR exome AF: 0.149

Gnomad4 AMR exome AF: 0.00921

Gnomad4 ASJ exome AF: 0.000673

Gnomad4 EAS exome AF: 0.000166

Gnomad4 SAS exome AF: 0.000390

Gnomad4 FIN exome AF: 0.0000252

Gnomad4 NFE exome AF: 0.000457

Gnomad4 OTH exome AF: 0.0108

GnomAD4 genome AF: 0.0411 AC: 4602 AN: 112064 Hom.: 233 Cov.: 23 AF XY: 0.0359 AC XY: 1232 AN XY: 34288

Gnomad4 AFR AF: 0.140

Gnomad4 AMR AF: 0.0191

Gnomad4 ASJ AF: 0.000378

Gnomad4 EAS AF: 0.000282

Gnomad4 SAS AF: 0.000739

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000676

Gnomad4 OTH AF: 0.0314

Alfa AF: 0.00212 Hom.: 14

Bravo AF: 0.0483

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Granulomatous disease, chronic, X-linked Benign:2

Benign, criteria provided, single submitter	clinical testing;curation	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Aug 18, 2011	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.24
DANN	Benign	0.60

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

Other links and lift over

dbSNP: rs34834015; hg19: chrX-37664440;