rs4673

Variant names:

• chr16-88646828-A-C
• NM_000101.4:c.214T>G

Your query was ambiguous. Multiple possible variants found:

• chr16-88646828-A-C
• chr16-88646828-A-G
• chr16-88646828-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000101.4(CYBA):​c.214T>G​(p.Tyr72Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y72H) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CYBA NM_000101.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.22

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYBA	NM_000101.4	c.214T>G	p.Tyr72Asp	missense_variant	Exon 4 of 6	ENST00000261623.8	NP_000092.2
CYBA	XM_011522905.4	c.214T>G	p.Tyr72Asp	missense_variant	Exon 4 of 6		XP_011521207.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYBA	ENST00000261623.8	c.214T>G	p.Tyr72Asp	missense_variant	Exon 4 of 6	1	NM_000101.4	ENSP00000261623.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.84e-7 AC: 1 AN: 1461290 Hom.: 0 Cov.: 44 AF XY: 0.00000138 AC XY: 1 AN XY: 726996

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Benign	-0.071	T
BayesDel_noAF	Uncertain	0.10
CADD	Uncertain	23
DANN	Uncertain	0.99
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Pathogenic	0.98	D
M_CAP	Pathogenic	0.59	D
MetaRNN	Uncertain	0.73	D
PROVEAN	Pathogenic	-7.0	D
MVP		0.66
ClinPred		0.99	D
GERP RS		3.5

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-88713236;