2-72132353-G-C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_019885.4(CYP26B1):ā€‹c.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

Scores

1
7
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.26
Variant links:
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]

Genome browser will be placed here

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
CYP26B1NM_019885.4 linkuse as main transcriptc.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
CYP26B1ENST00000001146.7 linkuse as main transcriptc.1413C>G p.Phe471Leu missense_variant 6/61 NM_019885.4 ENSP00000001146 P1Q9NR63-1
CYP26B1ENST00000546307.5 linkuse as main transcriptc.1188C>G p.Phe396Leu missense_variant 5/51 ENSP00000443304 Q9NR63-2
CYP26B1ENST00000412253.1 linkuse as main transcriptc.840C>G p.Phe280Leu missense_variant 5/51 ENSP00000401465

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152194
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0000941
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000811
AC:
2
AN:
246560
Hom.:
0
AF XY:
0.0000150
AC XY:
2
AN XY:
133672
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000548
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000481
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000130
AC:
19
AN:
1458820
Hom.:
0
Cov.:
32
AF XY:
0.0000110
AC XY:
8
AN XY:
725194
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000253
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.000132
Gnomad4 NFE exome
AF:
0.00000991
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152194
Hom.:
0
Cov.:
33
AF XY:
0.0000269
AC XY:
2
AN XY:
74346
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000941
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000540
Hom.:
0
ExAC
AF:
0.0000165
AC:
2

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 submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpDec 07, 2023This 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.86
BayesDel_addAF
Benign
-0.077
T
BayesDel_noAF
Benign
-0.18
CADD
Uncertain
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.18
.;T;.
Eigen
Benign
-0.30
Eigen_PC
Benign
-0.096
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Benign
0.76
T;T;T
M_CAP
Benign
0.034
D
MetaRNN
Benign
0.23
T;T;T
MetaSVM
Benign
-0.96
T
MutationAssessor
Uncertain
2.1
.;M;.
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Uncertain
0.72
T
PROVEAN
Uncertain
-2.5
N;N;D
REVEL
Uncertain
0.29
Sift
Benign
0.23
T;T;T
Sift4G
Uncertain
0.017
D;D;T
Polyphen
0.12
.;B;.
Vest4
0.44
MutPred
0.41
.;Loss of sheet (P = 0.1907);.;
MVP
0.44
MPC
0.93
ClinPred
0.87
D
GERP RS
4.8
Varity_R
0.29
gMVP
0.82

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs764995614; hg19: chr2-72359482; API