X-37799202-A-G

Variant names:

• chrX-37799202-A-G
• rs5964125
• NM_000397.4:c.804+118A>G

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.804+118A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 698,190 control chromosomes in the GnomAD database, including 7,066 homozygotes. There are 35,503 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (1072 hom., 5460 hem., cov: 23)
  • Exomes 𝑓: 0.17 (5994 hom. 30043 hem.)
• Consequence: CYBB NM_000397.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.38
• Publications: 5 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=-0.8).
• BP6: Variant X-37799202-A-G is Benign according to our data. Variant chrX-37799202-A-G is described in ClinVar as Benign. ClinVar VariationId is 1185172.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.181 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.804+118A>G		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.804+118A>G		intron	N/A	ENSP00000367851.4
	ENSG00000250349	ENST00000465127.1	TSL:5	c.171+373202A>G		intron	N/A	ENSP00000417050.1
	CYBB	ENST00000696171.1		c.708+118A>G		intron	N/A	ENSP00000512462.1

Frequencies

GnomAD3 genomes AF: 0.165 AC: 18431 AN: 111711 Hom.: 1069 Cov.: 23

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.200

Gnomad EAS AF: 0.0674

Gnomad SAS AF: 0.193

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.0928

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.145

GnomAD4 exome AF: 0.170 AC: 99980 AN: 586426 Hom.: 5994 AF XY: 0.185 AC XY: 30043 AN XY: 162768

African (AFR) AF: 0.201 AC: 3207 AN: 15973

American (AMR) AF: 0.184 AC: 5628 AN: 30533

Ashkenazi Jewish (ASJ) AF: 0.224 AC: 3480 AN: 15518

East Asian (EAS) AF: 0.0486 AC: 1271 AN: 26176

South Asian (SAS) AF: 0.202 AC: 8279 AN: 40944

European-Finnish (FIN) AF: 0.153 AC: 5352 AN: 34885

Middle Eastern (MID) AF: 0.127 AC: 313 AN: 2467

European-Non Finnish (NFE) AF: 0.173 AC: 67730 AN: 391106

Other (OTH) AF: 0.164 AC: 4720 AN: 28824

GnomAD4 genome AF: 0.165 AC: 18443 AN: 111764 Hom.: 1072 Cov.: 23 AF XY: 0.160 AC XY: 5460 AN XY: 34034

African (AFR) AF: 0.185 AC: 5682 AN: 30790

American (AMR) AF: 0.176 AC: 1857 AN: 10546

Ashkenazi Jewish (ASJ) AF: 0.200 AC: 528 AN: 2641

East Asian (EAS) AF: 0.0667 AC: 237 AN: 3552

South Asian (SAS) AF: 0.194 AC: 532 AN: 2737

European-Finnish (FIN) AF: 0.134 AC: 814 AN: 6074

Middle Eastern (MID) AF: 0.0926 AC: 20 AN: 216

European-Non Finnish (NFE) AF: 0.160 AC: 8479 AN: 53015

Other (OTH) AF: 0.148 AC: 224 AN: 1511

Alfa AF: 0.168 Hom.: 3659

Bravo AF: 0.169

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Granulomatous disease, chronic, X-linked (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	9.0
DANN	Benign	0.85
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: rs5964125; hg19: chrX-37658455;