rs4782308

Variant names:

• chr16-88647065-G-A
• rs4782308
• NM_000101.4:c.203+36C>T

Your query was ambiguous. Multiple possible variants found:

• chr16-88647065-G-A
• chr16-88647065-G-C

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+36C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.665 in 1,580,492 control chromosomes in the GnomAD database, including 353,172 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.64 (31958 hom., cov: 33)
  • Exomes 𝑓: 0.67 (321214 hom.)
• Consequence: CYBA NM_000101.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.00300
• Publications: 13 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=-0.82).
• BP6: Variant 16-88647065-G-A is Benign according to our data. Variant chr16-88647065-G-A is described in ClinVar as Benign. ClinVar VariationId is 1172931.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.842 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+36C>T		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+36C>T		intron	N/A	ENSP00000261623.3	P13498
	CYBA	ENST00000569359.5	TSL:1	c.203+36C>T		intron	N/A	ENSP00000456079.1	H3BR52
	CYBA	ENST00000696161.1		c.203+36C>T		intron	N/A	ENSP00000512451.1	A0A8Q3WL26

Frequencies

GnomAD3 genomes AF: 0.642 AC: 97613 AN: 151952 Hom.: 31936 Cov.: 33

Gnomad AFR AF: 0.522

Gnomad AMI AF: 0.689

Gnomad AMR AF: 0.717

Gnomad ASJ AF: 0.567

Gnomad EAS AF: 0.862

Gnomad SAS AF: 0.620

Gnomad FIN AF: 0.819

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.660

Gnomad OTH AF: 0.625

GnomAD2 exomes AF: 0.680 AC: 152263 AN: 223910 AF XY: 0.672

Gnomad AFR exome AF: 0.523

Gnomad AMR exome AF: 0.764

Gnomad ASJ exome AF: 0.554

Gnomad EAS exome AF: 0.856

Gnomad FIN exome AF: 0.812

Gnomad NFE exome AF: 0.657

Gnomad OTH exome AF: 0.648

GnomAD4 exome AF: 0.668 AC: 953492 AN: 1428422 Hom.: 321214 Cov.: 27 AF XY: 0.666 AC XY: 473340 AN XY: 711196

African (AFR) AF: 0.520 AC: 17063 AN: 32830

American (AMR) AF: 0.753 AC: 32353 AN: 42952

Ashkenazi Jewish (ASJ) AF: 0.570 AC: 14730 AN: 25850

East Asian (EAS) AF: 0.862 AC: 33537 AN: 38928

South Asian (SAS) AF: 0.616 AC: 52192 AN: 84758

European-Finnish (FIN) AF: 0.806 AC: 38239 AN: 47472

Middle Eastern (MID) AF: 0.564 AC: 3225 AN: 5714

European-Non Finnish (NFE) AF: 0.663 AC: 723194 AN: 1090618

Other (OTH) AF: 0.657 AC: 38959 AN: 59300

GnomAD4 genome AF: 0.642 AC: 97674 AN: 152070 Hom.: 31958 Cov.: 33 AF XY: 0.651 AC XY: 48376 AN XY: 74338

African (AFR) AF: 0.521 AC: 21617 AN: 41452

American (AMR) AF: 0.717 AC: 10958 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.567 AC: 1966 AN: 3470

East Asian (EAS) AF: 0.863 AC: 4448 AN: 5156

South Asian (SAS) AF: 0.621 AC: 2994 AN: 4824

European-Finnish (FIN) AF: 0.819 AC: 8691 AN: 10608

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.660 AC: 44890 AN: 67966

Other (OTH) AF: 0.626 AC: 1322 AN: 2112

Alfa AF: 0.633 Hom.: 5525

Bravo AF: 0.632

Asia WGS AF: 0.713 AC: 2480 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.2
DANN	Benign	0.84
PhyloP100		-0.0030
PromoterAI		0.018	Neutral
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.3
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: rs4782308; hg19: chr16-88713473;