rs7059081

Variant names:

• chrX-37782231-C-G
• rs7059081
• NM_000397.4:c.141+48C>G

Your query was ambiguous. Multiple possible variants found:

• chrX-37782231-C-G
• chrX-37782231-C-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.141+48C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0664 in 842,855 control chromosomes in the GnomAD database, including 1,519 homozygotes. There are 15,643 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.052 (163 hom., 1612 hem., cov: 22)
  • Exomes 𝑓: 0.069 (1356 hom. 14031 hem.)
• Consequence: CYBB NM_000397.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0380
• Publications: 3 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=-0.81).
• BP6: Variant X-37782231-C-G is Benign according to our data. Variant chrX-37782231-C-G is described in ClinVar as Benign. ClinVar VariationId is 1246166.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0756 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYBB	NM_000397.4	c.141+48C>G		intron_variant	Intron 2 of 12	ENST00000378588.5	NP_000388.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYBB	ENST00000378588.5	c.141+48C>G		intron_variant	Intron 2 of 12	1	NM_000397.4	ENSP00000367851.4
ENSG00000250349	ENST00000465127.1	c.171+356231C>G		intron_variant	Intron 3 of 8	5		ENSP00000417050.1

Frequencies

GnomAD3 genomes AF: 0.0517 AC: 5785 AN: 111970 Hom.: 163 Cov.: 22

Gnomad AFR AF: 0.0101

Gnomad AMI AF: 0.0675

Gnomad AMR AF: 0.0529

Gnomad ASJ AF: 0.0740

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0125

Gnomad FIN AF: 0.0699

Gnomad MID AF: 0.0464

Gnomad NFE AF: 0.0775

Gnomad OTH AF: 0.0554

GnomAD2 exomes AF: 0.0508 AC: 8848 AN: 174201 AF XY: 0.0494

Gnomad AFR exome AF: 0.00942

Gnomad AMR exome AF: 0.0322

Gnomad ASJ exome AF: 0.0724

Gnomad EAS exome AF: 0.000898

Gnomad FIN exome AF: 0.0727

Gnomad NFE exome AF: 0.0750

Gnomad OTH exome AF: 0.0633

GnomAD4 exome AF: 0.0687 AC: 50214 AN: 730831 Hom.: 1356 Cov.: 13 AF XY: 0.0694 AC XY: 14031 AN XY: 202299

African (AFR) AF: 0.0117 AC: 222 AN: 18903

American (AMR) AF: 0.0345 AC: 1186 AN: 34398

Ashkenazi Jewish (ASJ) AF: 0.0704 AC: 1202 AN: 17066

East Asian (EAS) AF: 0.000281 AC: 8 AN: 28434

South Asian (SAS) AF: 0.0142 AC: 660 AN: 46529

European-Finnish (FIN) AF: 0.0751 AC: 2931 AN: 39044

Middle Eastern (MID) AF: 0.0350 AC: 120 AN: 3428

European-Non Finnish (NFE) AF: 0.0818 AC: 41638 AN: 509241

Other (OTH) AF: 0.0665 AC: 2247 AN: 33788

GnomAD4 genome AF: 0.0516 AC: 5782 AN: 112024 Hom.: 163 Cov.: 22 AF XY: 0.0471 AC XY: 1612 AN XY: 34212

African (AFR) AF: 0.0101 AC: 311 AN: 30869

American (AMR) AF: 0.0527 AC: 560 AN: 10619

Ashkenazi Jewish (ASJ) AF: 0.0740 AC: 196 AN: 2650

East Asian (EAS) AF: 0.00 AC: 0 AN: 3571

South Asian (SAS) AF: 0.0125 AC: 34 AN: 2714

European-Finnish (FIN) AF: 0.0699 AC: 421 AN: 6026

Middle Eastern (MID) AF: 0.0415 AC: 9 AN: 217

European-Non Finnish (NFE) AF: 0.0775 AC: 4121 AN: 53143

Other (OTH) AF: 0.0548 AC: 84 AN: 1534

Alfa AF: 0.0612 Hom.: 523

Bravo AF: 0.0500

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.7
DANN	Benign	0.69
PhyloP100		0.038
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs7059081; hg19: chrX-37641484;