rs4673
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000101.4(CYBA):c.214T>C(p.Tyr72His) variant causes a missense change. The variant allele was found at a frequency of 0.672 in 1,612,206 control chromosomes in the GnomAD database, including 367,613 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
NM_000101.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.653 AC: 99158AN: 151878Hom.: 32915 Cov.: 32
GnomAD3 exomes AF: 0.698 AC: 174863AN: 250626Hom.: 62429 AF XY: 0.690 AC XY: 93689AN XY: 135686
GnomAD4 exome AF: 0.674 AC: 983701AN: 1460210Hom.: 334674 Cov.: 44 AF XY: 0.672 AC XY: 488360AN XY: 726538
GnomAD4 genome AF: 0.653 AC: 99225AN: 151996Hom.: 32939 Cov.: 32 AF XY: 0.661 AC XY: 49133AN XY: 74292
ClinVar
Submissions by phenotype
not specified Benign:5
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Variant summary: CYBA c.214T>C (p.Tyr72His) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.7 in 250626 control chromosomes, suggesting that it is the major allele and therefore benign. The observed variant frequency is approximately 1139 fold of the estimated maximal expected allele frequency for a pathogenic variant in CYBA causing Chronic Granulomatous Disease phenotype (0.00061), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.214T>C in individuals affected with Chronic Granulomatous Disease and no experimental evidence demonstrating its impact on protein function have been reported. Five ClinVar submitters have assessed the clinical significance of this variant after 2014: four have classified the variant as benign and one as likely pathogenic. Based on the evidence outlined above, the variant was classified as benign. -
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This variant is classified as Benign based on local population frequency. This variant was detected in 93% of patients studied by a panel of primary immunodeficiencies. Number of patients: 88. Only high quality variants are reported. -
Granulomatous disease, chronic, autosomal recessive, cytochrome b-negative Benign:3
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not provided Benign:2Other:1
Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing. -
This variant is associated with the following publications: (PMID: 30709874, 17383305, 21884584, 18799874, 19689263, 11023926, 15078863, 23821607, 22396743, 23409188, 25095657, 23040216, 9445163, 24339896, 24392120, 29132304, 29454792) -
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Very early onset inflammatory bowel disease Pathogenic:1
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Chronic granulomatous disease Benign:1
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CYBA POLYMORPHISM Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at