2-171554814-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The ENST00000321348.9(CYBRD1):c.848G>A(p.Arg283Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000372 in 1,612,986 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000027 ( 0 hom. )
Consequence
CYBRD1
ENST00000321348.9 missense
ENST00000321348.9 missense
Scores
2
3
14
Clinical Significance
Conservation
PhyloP100: 4.52
Genes affected
CYBRD1 (HGNC:20797): (cytochrome b reductase 1) This gene is a member of the cytochrome b(561) family that encodes an iron-regulated protein. It highly expressed in the duodenal brush border membrane. It has ferric reductase activity and is believed to play a physiological role in dietary iron absorption. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.14567533).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CYBRD1 | NM_024843.4 | c.848G>A | p.Arg283Lys | missense_variant | 4/4 | ENST00000321348.9 | NP_079119.3 | |
CYBRD1 | NM_001256909.2 | c.674G>A | p.Arg225Lys | missense_variant | 4/4 | NP_001243838.1 | ||
CYBRD1 | NM_001127383.2 | c.*165G>A | 3_prime_UTR_variant | 3/3 | NP_001120855.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CYBRD1 | ENST00000321348.9 | c.848G>A | p.Arg283Lys | missense_variant | 4/4 | 1 | NM_024843.4 | ENSP00000319141 | P1 | |
CYBRD1 | ENST00000375252.3 | c.*165G>A | 3_prime_UTR_variant | 3/3 | 1 | ENSP00000364401 | ||||
CYBRD1 | ENST00000409484.5 | c.674G>A | p.Arg225Lys | missense_variant | 4/4 | 2 | ENSP00000386739 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152212Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250506Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135416
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GnomAD4 exome AF: 0.00000274 AC: 4AN: 1460774Hom.: 0 Cov.: 33 AF XY: 0.00000413 AC XY: 3AN XY: 726716
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GnomAD4 genome AF: 0.0000131 AC: 2AN: 152212Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74362
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 30, 2023 | The c.848G>A (p.R283K) alteration is located in exon 4 (coding exon 4) of the CYBRD1 gene. This alteration results from a G to A substitution at nucleotide position 848, causing the arginine (R) at amino acid position 283 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
.;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T
M_CAP
Benign
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
.;M
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Pathogenic
D;D
Sift4G
Pathogenic
D;D
Polyphen
0.058
.;B
Vest4
MutPred
0.31
.;Gain of ubiquitination at R283 (P = 0.0045);
MVP
MPC
0.43
ClinPred
T
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at