2-72132353-G-C
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_019885.4(CYP26B1):āc.1413C>Gā(p.Phe471Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000013 in 1,611,014 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000013 ( 0 hom., cov: 33)
Exomes š: 0.000013 ( 0 hom. )
Consequence
CYP26B1
NM_019885.4 missense
NM_019885.4 missense
Scores
1
7
11
Clinical Significance
Conservation
PhyloP100: 4.26
Genes affected
CYP26B1 (HGNC:20581): (cytochrome P450 family 26 subfamily B member 1) This gene encodes a member of the cytochrome P450 superfamily. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. The encoded protein is localized to the endoplasmic reticulum, and functions as a critical regulator of all-trans retinoic acid levels by the specific inactivation of all-trans retinoic acid to hydroxylated forms. Mutations in this gene are associated with radiohumeral fusions and other skeletal and craniofacial anomalies, and increased levels of the encoded protein are associated with atherosclerotic lesions. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2013]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.2343567).
BS2
High AC in GnomAdExome4 at 19 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CYP26B1 | NM_019885.4 | c.1413C>G | p.Phe471Leu | missense_variant | 6/6 | ENST00000001146.7 | NP_063938.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CYP26B1 | ENST00000001146.7 | c.1413C>G | p.Phe471Leu | missense_variant | 6/6 | 1 | NM_019885.4 | ENSP00000001146 | P1 | |
CYP26B1 | ENST00000546307.5 | c.1188C>G | p.Phe396Leu | missense_variant | 5/5 | 1 | ENSP00000443304 | |||
CYP26B1 | ENST00000412253.1 | c.840C>G | p.Phe280Leu | missense_variant | 5/5 | 1 | ENSP00000401465 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152194Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00000811 AC: 2AN: 246560Hom.: 0 AF XY: 0.0000150 AC XY: 2AN XY: 133672
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GnomAD4 exome AF: 0.0000130 AC: 19AN: 1458820Hom.: 0 Cov.: 32 AF XY: 0.0000110 AC XY: 8AN XY: 725194
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GnomAD4 genome AF: 0.0000131 AC: 2AN: 152194Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74346
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 07, 2023 | This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 471 of the CYP26B1 protein (p.Phe471Leu). This variant is present in population databases (rs764995614, gnomAD 0.005%). This variant has not been reported in the literature in individuals affected with CYP26B1-related conditions. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
.;T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T
M_CAP
Benign
D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
.;M;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
N;N;D
REVEL
Uncertain
Sift
Benign
T;T;T
Sift4G
Uncertain
D;D;T
Polyphen
0.12
.;B;.
Vest4
MutPred
0.41
.;Loss of sheet (P = 0.1907);.;
MVP
MPC
0.93
ClinPred
D
GERP RS
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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