Genetic Variant CYP26B1:c.*2907C>A (chr2-72129320-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_019885.4(CYP26B1):c.*2907C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 152,230 control chromosomes in the GnomAD database, including 12,923 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 0.35 ( 12914 hom., cov: 33)

Exomes 𝑓: 0.20 ( 9 hom. )

Consequence

CYP26B1
NM_019885.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.16

Publications

12 publications found

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]

CYP26B1 Gene-Disease associations (from GenCC):

lethal occipital encephalocele-skeletal dysplasia syndrome
Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet, PanelApp Australia

CYP26B1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.676 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP26B1	NM_019885.4 link	c.*2907C>A		3_prime_UTR_variant	Exon 6 of 6	ENST00000001146.7	NP_063938.1	Q9NR63-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CYP26B1	ENST00000001146.7 link	c.*2907C>A	3_prime_UTR_variant	Exon 6 of 6	1	NM_019885.4	ENSP00000001146.2	Q9NR63-1
CYP26B1	ENST00000546307.5 link	c.*2907C>A	3_prime_UTR_variant	Exon 5 of 5	1		ENSP00000443304.1	Q9NR63-2
CYP26B1	ENST00000412253.1 link	c.*2907C>A	downstream_gene_variant		1		ENSP00000401465.1	E7ER08

Frequencies

GnomAD3 genomes

AF:

0.348

AC:

52840

AN:

151728

Hom.:

12875

Cov.:

show subpopulations

Gnomad AFR

AF:

0.682

Gnomad AMI

AF:

0.0945

Gnomad AMR

AF:

0.298

Gnomad ASJ

AF:

0.261

Gnomad EAS

AF:

0.549

Gnomad SAS

AF:

0.295

Gnomad FIN

AF:

0.174

Gnomad MID

AF:

0.275

Gnomad NFE

AF:

0.182

Gnomad OTH

AF:

0.306

GnomAD4 exome

AF:

0.204

AC:

AN:

378

Hom.:

Cov.:

AF XY:

0.188

AC XY:

AN XY:

224

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.206

AC:

AN:

374

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.349

AC:

52939

AN:

151852

Hom.:

12914

Cov.:

AF XY:

0.345

AC XY:

25639

AN XY:

74232

show subpopulations

African (AFR)

AF:

0.682

AC:

28277

AN:

41434

American (AMR)

AF:

0.298

AC:

4540

AN:

15244

Ashkenazi Jewish (ASJ)

AF:

0.261

AC:

905

AN:

3470

East Asian (EAS)

AF:

0.548

AC:

2817

AN:

5138

South Asian (SAS)

AF:

0.293

AC:

1396

AN:

4762

European-Finnish (FIN)

AF:

0.174

AC:

1835

AN:

10568

Middle Eastern (MID)

AF:

0.293

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.182

AC:

12336

AN:

67916

Other (OTH)

AF:

0.312

AC:

661

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1404

2809

4213

5618

7022

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

466

932

1398

1864

2330

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.227

Hom.:

11436

Bravo

AF:

0.373

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Benign

0.82

PhyloP100

2.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over