17-82450939-C-T

Variant names:

• chr17-82450939-C-T
• rs9303029
• ENST00000658363.1:n.29C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000658363.1(ENSG00000287193):​n.29C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 152,028 control chromosomes in the GnomAD database, including 2,690 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 0.18 (2690 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ENSG00000287193 ENST00000658363.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.97
• Publications: 22 publications found

Genes affected

ENSG00000287193 (HGNC:):

CYBC1 (HGNC:28672): (cytochrome b-245 chaperone 1) Involved in innate immune response and respiratory burst after phagocytosis. Located in endoplasmic reticulum. Implicated in chronic granulomatous disease. [provided by Alliance of Genome Resources, Apr 2022]

CYBC1 Gene-Disease associations (from GenCC):

• granulomatous disease, chronic, autosomal recessive, 5

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• chronic granulomatous disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYBC1	NM_001033046.4	c.-278G>A		upstream_gene_variant		ENST00000306645.10	NP_001028218.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYBC1	ENST00000306645.10	c.-278G>A		upstream_gene_variant		1	NM_001033046.4	ENSP00000307765.5

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26695 AN: 151912 Hom.: 2672 Cov.: 32

Gnomad AFR AF: 0.214

Gnomad AMI AF: 0.0537

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.236

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.173

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.175

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 8 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 4

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 6

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.176 AC: 26772 AN: 152028 Hom.: 2690 Cov.: 32 AF XY: 0.181 AC XY: 13419 AN XY: 74328

African (AFR) AF: 0.215 AC: 8903 AN: 41464

American (AMR) AF: 0.283 AC: 4320 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 402 AN: 3468

East Asian (EAS) AF: 0.235 AC: 1213 AN: 5162

South Asian (SAS) AF: 0.244 AC: 1173 AN: 4814

European-Finnish (FIN) AF: 0.173 AC: 1826 AN: 10572

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.124 AC: 8455 AN: 67974

Other (OTH) AF: 0.180 AC: 380 AN: 2106

Alfa AF: 0.138 Hom.: 4614

Bravo AF: 0.185

Asia WGS AF: 0.262 AC: 910 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.1
DANN	Benign	0.83
PhyloP100		-2.0
PromoterAI		-0.034	Neutral

Splicing

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

Other links and lift over

dbSNP: rs9303029; hg19: chr17-80408815;