NM_000101.4:c.549C>T

Variant names:

• chr16-88643392-G-A
• rs1327160850
• NM_000101.4:c.549C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_000101.4(CYBA):​c.549C>T​(p.Pro183Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000724 in 1,381,988 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P183P) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: CYBA NM_000101.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.38
• Publications: 2 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP7: Synonymous conserved (PhyloP=1.38 with no splicing effect.

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.549C>T	p.Pro183Pro	synonymous	Exon 6 of 6	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.549C>T	p.Pro183Pro	synonymous	Exon 6 of 6	ENSP00000261623.3	P13498
	CYBA	ENST00000696161.1		c.679C>T	p.Pro227Ser	missense	Exon 6 of 6	ENSP00000512451.1	A0A8Q3WL26
	CYBA	ENST00000967613.1		c.597C>T	p.Pro199Pro	synonymous	Exon 7 of 7	ENSP00000637672.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.24e-7 AC: 1 AN: 1381988 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 681736

African (AFR) AF: 0.00 AC: 0 AN: 29736

American (AMR) AF: 0.00 AC: 0 AN: 34958

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24760

East Asian (EAS) AF: 0.00 AC: 0 AN: 34632

South Asian (SAS) AF: 0.00 AC: 0 AN: 78320

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42144

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4914

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1075130

Other (OTH) AF: 0.0000174 AC: 1 AN: 57394

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	4.9
DANN	Benign	0.84
PhyloP100		1.4
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.7

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: rs1327160850; hg19: chr16-88709800;