rs4782393

Variant names:

• chr16-88647093-A-G
• rs4782393
• NM_000101.4:c.203+8T>C

Your query was ambiguous. Multiple possible variants found:

• chr16-88647093-A-G
• chr16-88647093-A-T

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.203+8T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.495 in 1,606,018 control chromosomes in the GnomAD database, including 201,103 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.44 (15338 hom., cov: 33)
  • Exomes 𝑓: 0.50 (185765 hom.)
• Consequence: CYBA NM_000101.4 splice_region, intron
• Scores: Splicing: ADA: 0.00001193
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9 O:1
• Conservation: PhyloP100: -3.29
• Publications: 14 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=-0.91).
• BP6: Variant 16-88647093-A-G is Benign according to our data. Variant chr16-88647093-A-G is described in ClinVar as Benign. ClinVar VariationId is 196207.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.507 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.203+8T>C		splice_region intron	N/A	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.203+8T>C		splice_region intron	N/A	ENSP00000261623.3	P13498
	CYBA	ENST00000569359.5	TSL:1	c.203+8T>C		splice_region intron	N/A	ENSP00000456079.1	H3BR52
	CYBA	ENST00000696161.1		c.203+8T>C		splice_region intron	N/A	ENSP00000512451.1	A0A8Q3WL26

Frequencies

GnomAD3 genomes AF: 0.440 AC: 66881 AN: 151974 Hom.: 15322 Cov.: 33

Gnomad AFR AF: 0.310

Gnomad AMI AF: 0.507

Gnomad AMR AF: 0.490

Gnomad ASJ AF: 0.414

Gnomad EAS AF: 0.243

Gnomad SAS AF: 0.447

Gnomad FIN AF: 0.519

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.511

Gnomad OTH AF: 0.436

GnomAD2 exomes AF: 0.471 AC: 113926 AN: 241700 AF XY: 0.471

Gnomad AFR exome AF: 0.306

Gnomad AMR exome AF: 0.545

Gnomad ASJ exome AF: 0.394

Gnomad EAS exome AF: 0.248

Gnomad FIN exome AF: 0.526

Gnomad NFE exome AF: 0.510

Gnomad OTH exome AF: 0.464

GnomAD4 exome AF: 0.500 AC: 727537 AN: 1453926 Hom.: 185765 Cov.: 33 AF XY: 0.499 AC XY: 361289 AN XY: 723468

African (AFR) AF: 0.301 AC: 10044 AN: 33386

American (AMR) AF: 0.536 AC: 23760 AN: 44364

Ashkenazi Jewish (ASJ) AF: 0.401 AC: 10463 AN: 26086

East Asian (EAS) AF: 0.211 AC: 8371 AN: 39580

South Asian (SAS) AF: 0.461 AC: 39624 AN: 86000

European-Finnish (FIN) AF: 0.530 AC: 26535 AN: 50106

Middle Eastern (MID) AF: 0.367 AC: 2114 AN: 5760

European-Non Finnish (NFE) AF: 0.521 AC: 577926 AN: 1108478

Other (OTH) AF: 0.477 AC: 28700 AN: 60166

GnomAD4 genome AF: 0.440 AC: 66918 AN: 152092 Hom.: 15338 Cov.: 33 AF XY: 0.438 AC XY: 32557 AN XY: 74358

African (AFR) AF: 0.310 AC: 12838 AN: 41478

American (AMR) AF: 0.491 AC: 7497 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.414 AC: 1435 AN: 3470

East Asian (EAS) AF: 0.243 AC: 1257 AN: 5170

South Asian (SAS) AF: 0.448 AC: 2158 AN: 4820

European-Finnish (FIN) AF: 0.519 AC: 5490 AN: 10580

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.511 AC: 34760 AN: 67978

Other (OTH) AF: 0.438 AC: 924 AN: 2112

Alfa AF: 0.471 Hom.: 3212

Bravo AF: 0.432

Asia WGS AF: 0.339 AC: 1180 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	2	Granulomatous disease, chronic, autosomal recessive, cytochrome b-negative (2)
-	-	2	not provided (3)
-	-	1	Chronic granulomatous disease (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.59
DANN	Benign	0.43
PhyloP100		-3.3
PromoterAI		-0.0067	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000012
dbscSNV1_RF	Benign	0.0
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: rs4782393; hg19: chr16-88713501; COSMIC: COSV55369250; COSMIC: COSV55369250;