NM_000101.4:c.*24G>A

Variant names:

• chr16-88643329-C-T
• rs1049255
• NM_000101.4:c.*24G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000101.4(CYBA):​c.*24G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.5 in 1,467,476 control chromosomes in the GnomAD database, including 184,305 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.48 (17711 hom., cov: 32)
  • Exomes 𝑓: 0.50 (166594 hom.)
• Consequence: CYBA NM_000101.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.788
• Publications: 93 publications found

Genes affected

CYBA (HGNC:2577): (cytochrome b-245 alpha chain) Cytochrome b is comprised of a light chain (alpha) and a heavy chain (beta). This gene encodes the light, alpha subunit which has been proposed as a primary component of the microbicidal oxidase system of phagocytes. Mutations in this gene are associated with autosomal recessive chronic granulomatous disease (CGD), that is characterized by the failure of activated phagocytes to generate superoxide, which is important for the microbicidal activity of these cells. [provided by RefSeq, Jul 2008]

CYBA Gene-Disease associations (from GenCC):

• granulomatous disease, chronic, autosomal recessive, cytochrome b-negative

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

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 16-88643329-C-T is Benign according to our data. Variant chr16-88643329-C-T is described in ClinVar as Benign. ClinVar VariationId is 1166946.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.506 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000101.4. 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
	CYBA	NM_000101.4	MANE Select	c.*24G>A		3_prime_UTR	Exon 6 of 6	NP_000092.2	P13498

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYBA	ENST00000261623.8	TSL:1 MANE Select	c.*24G>A		3_prime_UTR	Exon 6 of 6	ENSP00000261623.3	P13498
	CYBA	ENST00000696161.1		c.742G>A	p.Ala248Thr	missense	Exon 6 of 6	ENSP00000512451.1	A0A8Q3WL26
	CYBA	ENST00000967613.1		c.*24G>A		3_prime_UTR	Exon 7 of 7	ENSP00000637672.1

Frequencies

GnomAD3 genomes AF: 0.481 AC: 72889 AN: 151662 Hom.: 17707 Cov.: 32

Gnomad AFR AF: 0.425

Gnomad AMI AF: 0.409

Gnomad AMR AF: 0.511

Gnomad ASJ AF: 0.580

Gnomad EAS AF: 0.407

Gnomad SAS AF: 0.514

Gnomad FIN AF: 0.451

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.510

Gnomad OTH AF: 0.490

GnomAD2 exomes AF: 0.492 AC: 46513 AN: 94542 AF XY: 0.496

Gnomad AFR exome AF: 0.438

Gnomad AMR exome AF: 0.483

Gnomad ASJ exome AF: 0.576

Gnomad EAS exome AF: 0.384

Gnomad FIN exome AF: 0.448

Gnomad NFE exome AF: 0.504

Gnomad OTH exome AF: 0.500

GnomAD4 exome AF: 0.502 AC: 660123 AN: 1315698 Hom.: 166594 Cov.: 24 AF XY: 0.502 AC XY: 324850 AN XY: 646652

African (AFR) AF: 0.425 AC: 11208 AN: 26384

American (AMR) AF: 0.491 AC: 13471 AN: 27444

Ashkenazi Jewish (ASJ) AF: 0.580 AC: 13135 AN: 22636

East Asian (EAS) AF: 0.473 AC: 15328 AN: 32410

South Asian (SAS) AF: 0.517 AC: 37649 AN: 72764

European-Finnish (FIN) AF: 0.459 AC: 18086 AN: 39364

Middle Eastern (MID) AF: 0.558 AC: 2766 AN: 4954

European-Non Finnish (NFE) AF: 0.504 AC: 521452 AN: 1035148

Other (OTH) AF: 0.495 AC: 27028 AN: 54594

GnomAD4 genome AF: 0.481 AC: 72937 AN: 151778 Hom.: 17711 Cov.: 32 AF XY: 0.479 AC XY: 35547 AN XY: 74166

African (AFR) AF: 0.425 AC: 17598 AN: 41392

American (AMR) AF: 0.511 AC: 7818 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.580 AC: 2013 AN: 3470

East Asian (EAS) AF: 0.407 AC: 2085 AN: 5124

South Asian (SAS) AF: 0.515 AC: 2475 AN: 4808

European-Finnish (FIN) AF: 0.451 AC: 4762 AN: 10564

Middle Eastern (MID) AF: 0.592 AC: 174 AN: 294

European-Non Finnish (NFE) AF: 0.510 AC: 34613 AN: 67826

Other (OTH) AF: 0.488 AC: 1029 AN: 2108

Alfa AF: 0.508 Hom.: 37331

Bravo AF: 0.480

Asia WGS AF: 0.454 AC: 1578 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Granulomatous disease, chronic, autosomal recessive, cytochrome b-negative (2)
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.64
DANN	Benign	0.91
PhyloP100		-0.79
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

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: rs1049255; hg19: chr16-88709737; COSMIC: COSV54918632; COSMIC: COSV54918632;