rs5964151

Variant names:

• chrX-37811476-T-G
• rs5964151
• NM_000397.4:c.*559T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000397.4(CYBB):​c.*559T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 119,218 control chromosomes in the GnomAD database, including 2,188 homozygotes. There are 6,999 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.21 (2098 hom., 6680 hem., cov: 22)
  • Exomes 𝑓: 0.16 (90 hom. 319 hem.)
• Consequence: CYBB NM_000397.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38
• Publications: 7 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.343 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYBB	NM_000397.4	MANE Select	c.*559T>G		3_prime_UTR	Exon 13 of 13	NP_000388.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYBB	ENST00000378588.5	TSL:1 MANE Select	c.*559T>G		3_prime_UTR	Exon 13 of 13	ENSP00000367851.4
	ENSG00000250349	ENST00000465127.1	TSL:5	c.171+385476T>G		intron	N/A	ENSP00000417050.1
	CYBB	ENST00000968558.1		c.*26+533T>G		intron	N/A	ENSP00000638617.1

Frequencies

GnomAD3 genomes AF: 0.212 AC: 23526 AN: 110912 Hom.: 2098 Cov.: 22

Gnomad AFR AF: 0.348

Gnomad AMI AF: 0.0987

Gnomad AMR AF: 0.194

Gnomad ASJ AF: 0.200

Gnomad EAS AF: 0.0662

Gnomad SAS AF: 0.190

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.0979

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.187

GnomAD4 exome AF: 0.157 AC: 1298 AN: 8256 Hom.: 90 Cov.: 0 AF XY: 0.182 AC XY: 319 AN XY: 1748

African (AFR) AF: 0.276 AC: 8 AN: 29

American (AMR) AF: 0.186 AC: 256 AN: 1380

Ashkenazi Jewish (ASJ) AF: 0.208 AC: 11 AN: 53

East Asian (EAS) AF: 0.0826 AC: 36 AN: 436

South Asian (SAS) AF: 0.190 AC: 151 AN: 793

European-Finnish (FIN) AF: 0.139 AC: 23 AN: 165

Middle Eastern (MID) AF: 0.0714 AC: 1 AN: 14

European-Non Finnish (NFE) AF: 0.148 AC: 749 AN: 5045

Other (OTH) AF: 0.185 AC: 63 AN: 341

GnomAD4 genome AF: 0.212 AC: 23547 AN: 110962 Hom.: 2098 Cov.: 22 AF XY: 0.201 AC XY: 6680 AN XY: 33224

African (AFR) AF: 0.348 AC: 10597 AN: 30436

American (AMR) AF: 0.194 AC: 2026 AN: 10452

Ashkenazi Jewish (ASJ) AF: 0.200 AC: 527 AN: 2633

East Asian (EAS) AF: 0.0656 AC: 231 AN: 3524

South Asian (SAS) AF: 0.191 AC: 501 AN: 2621

European-Finnish (FIN) AF: 0.131 AC: 781 AN: 5976

Middle Eastern (MID) AF: 0.0981 AC: 21 AN: 214

European-Non Finnish (NFE) AF: 0.161 AC: 8508 AN: 52907

Other (OTH) AF: 0.189 AC: 288 AN: 1520

Alfa AF: 0.180 Hom.: 12850

Bravo AF: 0.225

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.075
DANN	Benign	0.77
PhyloP100		-1.4
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: rs5964151; hg19: chrX-37670729;