chr2-72134831-A-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_019885.4(CYP26B1):c.791T>C(p.Leu264Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 1,614,020 control chromosomes in the GnomAD database, including 23,829 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.19 ( 3216 hom., cov: 33)

Exomes 𝑓: 0.16 ( 20613 hom. )

Consequence

CYP26B1
NM_019885.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 2.56

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004927933).

BP6

Variant 2-72134831-A-G is Benign according to our data. Variant chr2-72134831-A-G is described in ClinVar as [Benign]. Clinvar id is 1180923.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP26B1	NM_019885.4 link	c.791T>C	p.Leu264Ser	missense_variant	Exon 4 of 6	ENST00000001146.7	NP_063938.1	Q9NR63-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CYP26B1	ENST00000001146.7 link	c.791T>C	p.Leu264Ser	missense_variant	Exon 4 of 6	1	NM_019885.4	ENSP00000001146.2	Q9NR63-1
CYP26B1	ENST00000546307.5 link	c.566T>C	p.Leu189Ser	missense_variant	Exon 3 of 5	1		ENSP00000443304.1	Q9NR63-2
CYP26B1	ENST00000412253.1 link	c.218T>C	p.Leu73Ser	missense_variant	Exon 3 of 5	1		ENSP00000401465.1	E7ER08
CYP26B1	ENST00000474509.1 link	c.*20T>C		downstream_gene_variant		4		ENSP00000430888.1	E5RHM2

Frequencies

GnomAD3 genomes

AF:

0.192

AC:

29139

AN:

152054

Hom.:

3187

Cov.:

show subpopulations

Gnomad AFR

AF:

0.290

Gnomad AMI

AF:

0.0604

Gnomad AMR

AF:

0.219

Gnomad ASJ

AF:

0.130

Gnomad EAS

AF:

0.0738

Gnomad SAS

AF:

0.0925

Gnomad FIN

AF:

0.142

Gnomad MID

AF:

0.146

Gnomad NFE

AF:

0.155

Gnomad OTH

AF:

0.182

GnomAD3 exomes

AF:

0.169

AC:

42396

AN:

251358

Hom.:

4391

AF XY:

0.159

AC XY:

21667

AN XY:

135852

show subpopulations

Gnomad AFR exome

AF:

0.293

Gnomad AMR exome

AF:

0.313

Gnomad ASJ exome

AF:

0.129

Gnomad EAS exome

AF:

0.0676

Gnomad SAS exome

AF:

0.0910

Gnomad FIN exome

AF:

0.142

Gnomad NFE exome

AF:

0.153

Gnomad OTH exome

AF:

0.161

GnomAD4 exome

AF:

0.162

AC:

236273

AN:

1461848

Hom.:

20613

Cov.:

AF XY:

0.158

AC XY:

114852

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.291

Gnomad4 AMR exome

AF:

0.303

Gnomad4 ASJ exome

AF:

0.128

Gnomad4 EAS exome

AF:

0.0773

Gnomad4 SAS exome

AF:

0.0928

Gnomad4 FIN exome

AF:

0.141

Gnomad4 NFE exome

AF:

0.162

Gnomad4 OTH exome

AF:

0.163

GnomAD4 genome

AF:

0.192

AC:

29213

AN:

152172

Hom.:

3216

Cov.:

AF XY:

0.189

AC XY:

14029

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.290

Gnomad4 AMR

AF:

0.219

Gnomad4 ASJ

AF:

0.130

Gnomad4 EAS

AF:

0.0737

Gnomad4 SAS

AF:

0.0909

Gnomad4 FIN

AF:

0.142

Gnomad4 NFE

AF:

0.155

Gnomad4 OTH

AF:

0.189

Alfa

AF:

0.161

Hom.:

5676

Bravo

AF:

0.206

TwinsUK

AF:

0.168

AC:

623

ALSPAC

AF:

0.162

AC:

624

ESP6500AA

AF:

0.282

AC:

1242

ESP6500EA

AF:

0.154

AC:

1321

ExAC

AF:

0.165

AC:

20000

Asia WGS

AF:

0.130

AC:

452

AN:

3478

EpiCase

AF:

0.156

EpiControl

AF:

0.162

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Nov 08, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 22415012) -

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.52

DEOGEN2

Benign

0.041

.;T;.

Eigen

Benign

-0.99

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.036

LIST_S2

Benign

0.0070

T;T;T

MetaRNN

Benign

0.0049

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.4

.;N;.

PrimateAI

Benign

0.45

PROVEAN

Benign

2.8

N;N;N

REVEL

Benign

0.058

Sift

Benign

0.86

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0

.;B;.

Vest4

0.033

MPC

0.39

ClinPred

0.0030

GERP RS

3.3

Varity_R

0.034

gMVP

0.17

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over