16-88646323-C-T

Position:

• chr16-88646323-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000261623.8(CYBA):​c.288-126G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00383 in 661,906 control chromosomes in the GnomAD database, including 173 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00027 (0 hom., cov: 35)
  • Exomes 𝑓: 0.0045 (173 hom.)
• Consequence: CYBA ENST00000261623.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.50

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000271 (27/99722) while in subpopulation AMR AF= 0.000504 (5/9928). AF 95% confidence interval is 0.000318. There are 0 homozygotes in gnomad4. There are 12 alleles in male gnomad4 subpopulation. Median coverage is 35. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 173 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYBA	NM_000101.4	c.288-126G>A		intron_variant		ENST00000261623.8	NP_000092.2
CYBA	XM_011522905.4	c.288-126G>A		intron_variant			XP_011521207.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYBA	ENST00000261623.8	c.288-126G>A		intron_variant		1	NM_000101.4	ENSP00000261623	P1

Frequencies

GnomAD3 genomes AF: 0.000271 AC: 27 AN: 99604 Hom.: 0 Cov.: 35

Gnomad AFR AF: 0.000502

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000504

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000149

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000107

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00446 AC: 2507 AN: 562184 Hom.: 173 Cov.: 8 AF XY: 0.00416 AC XY: 1225 AN XY: 294384

Gnomad4 AFR exome AF: 0.00165

Gnomad4 AMR exome AF: 0.00293

Gnomad4 ASJ exome AF: 0.00313

Gnomad4 EAS exome AF: 0.000100

Gnomad4 SAS exome AF: 0.00399

Gnomad4 FIN exome AF: 0.000939

Gnomad4 NFE exome AF: 0.00555

Gnomad4 OTH exome AF: 0.00352

GnomAD4 genome AF: 0.000271 AC: 27 AN: 99722 Hom.: 0 Cov.: 35 AF XY: 0.000243 AC XY: 12 AN XY: 49356

Gnomad4 AFR AF: 0.000500

Gnomad4 AMR AF: 0.000504

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000149

Gnomad4 NFE AF: 0.000107

Gnomad4 OTH AF: 0.00

Alfa AF: 0.182 Hom.: 375

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.8
DANN	Benign	0.54
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs13306294; hg19: chr16-88712731; COSMIC: COSV55367799; COSMIC: COSV55367799;