16-88651083-C-T

Variant names:

• chr16-88651083-C-T
• rs72550704
• ENST00000696163.1:c.-70G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The ENST00000696163.1(CYBA):​c.-70G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0147 in 1,466,256 control chromosomes in the GnomAD database, including 214 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0096 (7 hom., cov: 34)
  • Exomes 𝑓: 0.015 (207 hom.)
• Consequence: CYBA ENST00000696163.1 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.400
• Publications: 5 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=-0.8).
• BP6: Variant 16-88651083-C-T is Benign according to our data. Variant chr16-88651083-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 556199.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0096 (1457/151766) while in subpopulation NFE AF = 0.0155 (1050/67606). AF 95% confidence interval is 0.0148. There are 7 homozygotes in GnomAd4. There are 660 alleles in the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 7 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000696163.1. 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.-70G>A		upstream_gene	N/A	NP_000092.2	P13498

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYBA	ENST00000696163.1		c.-70G>A		5_prime_UTR	Exon 1 of 6	ENSP00000512453.1	A0A8Q3WL14
	CYBA	ENST00000261623.8	TSL:1 MANE Select	c.-70G>A		upstream_gene	N/A	ENSP00000261623.3	P13498
	CYBA	ENST00000569359.5	TSL:1	c.-70G>A		upstream_gene	N/A	ENSP00000456079.1	H3BR52

Frequencies

GnomAD3 genomes AF: 0.00961 AC: 1458 AN: 151654 Hom.: 7 Cov.: 34

Gnomad AFR AF: 0.00358

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.00289

Gnomad ASJ AF: 0.0121

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0151

Gnomad FIN AF: 0.00753

Gnomad MID AF: 0.0191

Gnomad NFE AF: 0.0155

Gnomad OTH AF: 0.00624

GnomAD4 exome AF: 0.0152 AC: 20042 AN: 1314490 Hom.: 207 Cov.: 22 AF XY: 0.0154 AC XY: 10049 AN XY: 651710

African (AFR) AF: 0.00240 AC: 72 AN: 29986

American (AMR) AF: 0.00339 AC: 120 AN: 35440

Ashkenazi Jewish (ASJ) AF: 0.0116 AC: 284 AN: 24554

East Asian (EAS) AF: 0.00 AC: 0 AN: 35266

South Asian (SAS) AF: 0.0137 AC: 1065 AN: 77630

European-Finnish (FIN) AF: 0.00986 AC: 368 AN: 37328

Middle Eastern (MID) AF: 0.0170 AC: 67 AN: 3942

European-Non Finnish (NFE) AF: 0.0171 AC: 17328 AN: 1015090

Other (OTH) AF: 0.0134 AC: 738 AN: 55254

GnomAD4 genome AF: 0.00960 AC: 1457 AN: 151766 Hom.: 7 Cov.: 34 AF XY: 0.00889 AC XY: 660 AN XY: 74234

African (AFR) AF: 0.00357 AC: 148 AN: 41512

American (AMR) AF: 0.00288 AC: 44 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.0121 AC: 42 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.0151 AC: 73 AN: 4828

European-Finnish (FIN) AF: 0.00753 AC: 80 AN: 10624

Middle Eastern (MID) AF: 0.0171 AC: 5 AN: 292

European-Non Finnish (NFE) AF: 0.0155 AC: 1050 AN: 67606

Other (OTH) AF: 0.00617 AC: 13 AN: 2106

Alfa AF: 0.0115 Hom.: 2

Bravo AF: 0.00880

Asia WGS AF: 0.00404 AC: 14 AN: 3476

ClinVar

ClinVar submissions

Significance: Likely 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)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.6
DANN	Benign	0.91
PhyloP100		-0.40
PromoterAI		-0.35	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=300/0	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: rs72550704; hg19: chr16-88717491;