NM_000397.4:c.1314+19C>T

Variant names:

• chrX-37805187-C-T
• rs34834015
• NM_000397.4:c.1314+19C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• granulomatous disease, chronic, X-linked

  Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• chronic granulomatous disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• X-linked Mendelian susceptibility to mycobacterial diseases due to CYBB deficiency

  Inheritance: XL, Unknown Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

ENSG00000250349 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000397.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYBB	NM_000397.4	MANE Select	c.1314+19C>T		intron	N/A	NP_000388.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYBB	ENST00000378588.5	TSL:1 MANE Select	c.1314+19C>T		intron	N/A	ENSP00000367851.4
	ENSG00000250349	ENST00000465127.1	TSL:5	c.171+379187C>T		intron	N/A	ENSP00000417050.1
	CYBB	ENST00000696171.1		c.1218+19C>T		intron	N/A	ENSP00000512462.1

Frequencies

GnomAD3 genomes AF: 0.0410 AC: 4594 AN: 112010 Hom.: 233 Cov.: 23

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

GnomAD2 exomes AF: 0.0119 AC: 2146 AN: 179935 AF XY: 0.00767

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 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

African (AFR) AF: 0.149 AC: 3902 AN: 26258

American (AMR) AF: 0.00921 AC: 323 AN: 35068

Ashkenazi Jewish (ASJ) AF: 0.000673 AC: 13 AN: 19314

East Asian (EAS) AF: 0.000166 AC: 5 AN: 30167

South Asian (SAS) AF: 0.000390 AC: 21 AN: 53856

European-Finnish (FIN) AF: 0.0000252 AC: 1 AN: 39722

Middle Eastern (MID) AF: 0.00727 AC: 30 AN: 4125

European-Non Finnish (NFE) AF: 0.000457 AC: 382 AN: 836732

Other (OTH) AF: 0.0108 AC: 493 AN: 45857

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

African (AFR) AF: 0.140 AC: 4307 AN: 30743

American (AMR) AF: 0.0191 AC: 203 AN: 10635

Ashkenazi Jewish (ASJ) AF: 0.000378 AC: 1 AN: 2648

East Asian (EAS) AF: 0.000282 AC: 1 AN: 3547

South Asian (SAS) AF: 0.000739 AC: 2 AN: 2707

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6133

Middle Eastern (MID) AF: 0.0185 AC: 4 AN: 216

European-Non Finnish (NFE) AF: 0.000676 AC: 36 AN: 53223

Other (OTH) AF: 0.0314 AC: 48 AN: 1529

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

Granulomatous disease, chronic, X-linked Benign:2

Aug 18, 2011

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing;curation

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not specified Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.24
DANN	Benign	0.60
PhyloP100		-0.68
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs34834015; hg19: chrX-37664440;