2-72132352-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_019885.4(CYP26B1):c.1414C>T(p.Pro472Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000597 in 1,611,066 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00060 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00060 ( 2 hom. )

Consequence

CYP26B1
NM_019885.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 8.07

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 was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005674988).

BP6

Variant 2-72132352-G-A is Benign according to our data. Variant chr2-72132352-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 1298811.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Benign=1}.

BS2

High AC in GnomAd4 at 92 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP26B1	NM_019885.4 link	c.1414C>T	p.Pro472Ser	missense_variant	Exon 6 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.1414C>T	p.Pro472Ser	missense_variant	Exon 6 of 6	1	NM_019885.4	ENSP00000001146.2	Q9NR63-1
CYP26B1	ENST00000546307.5 link	c.1189C>T	p.Pro397Ser	missense_variant	Exon 5 of 5	1		ENSP00000443304.1	Q9NR63-2
CYP26B1	ENST00000412253.1 link	c.841C>T	p.Pro281Ser	missense_variant	Exon 5 of 5	1		ENSP00000401465.1	E7ER08

Frequencies

GnomAD3 genomes

AF:

0.000604

AC:

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.0156

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000353

Gnomad OTH

AF:

0.00144

GnomAD2 exomes

AF:

0.00112

AC:

276

AN:

246506

AF XY:

0.00102

show subpopulations

Gnomad AFR exome

AF:

0.000127

Gnomad AMR exome

AF:

0.000439

Gnomad ASJ exome

AF:

0.0182

Gnomad EAS exome

AF:

0.000165

Gnomad FIN exome

AF:

0.0000481

Gnomad NFE exome

AF:

0.000602

Gnomad OTH exome

AF:

0.000999

GnomAD4 exome

AF:

0.000596

AC:

870

AN:

1458744

Hom.:

Cov.:

AF XY:

0.000605

AC XY:

439

AN XY:

725200

show subpopulations

Gnomad4 AFR exome

AF:

0.0000897

AC:

AN:

33434

Gnomad4 AMR exome

AF:

0.000292

AC:

AN:

44468

Gnomad4 ASJ exome

AF:

0.0170

AC:

443

AN:

26056

Gnomad4 EAS exome

AF:

0.000202

AC:

AN:

39580

Gnomad4 SAS exome

AF:

0.0000582

AC:

AN:

85962

Gnomad4 FIN exome

AF:

0.0000376

AC:

AN:

53178

Gnomad4 NFE exome

AF:

0.000273

AC:

303

AN:

1110076

Gnomad4 Remaining exome

AF:

0.00151

AC:

AN:

60224

Heterozygous variant carriers

109

163

218

272

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000604

AC:

AN:

152322

Hom.:

Cov.:

AF XY:

0.000698

AC XY:

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.000120

AC:

0.000120267

AN:

0.000120267

Gnomad4 AMR

AF:

0.000196

AC:

0.000196053

AN:

0.000196053

Gnomad4 ASJ

AF:

0.0156

AC:

0.015553

AN:

0.015553

Gnomad4 EAS

AF:

0.000386

AC:

0.00038625

AN:

0.00038625

Gnomad4 SAS

AF:

0.00

AC:

AN:

Gnomad4 FIN

AF:

0.0000941

AC:

0.0000941265

AN:

0.0000941265

Gnomad4 NFE

AF:

0.000353

AC:

0.000352796

AN:

0.000352796

Gnomad4 OTH

AF:

0.00142

AC:

0.00142315

AN:

0.00142315

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Variant carriers

<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:

0.00104

Hom.:

Bravo

AF:

0.000638

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00105

AC:

ExAC

AF:

0.000898

AC:

109

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:1

Oct 15, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aug 01, 2021

CeGaT Center for Human Genetics Tuebingen

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.54

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.12

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.47

.;T;.

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.89

D;D;D

M_CAP

Benign

0.049

MetaRNN

Benign

0.0057

T;T;T

MetaSVM

Benign

-0.47

MutationAssessor

Uncertain

2.3

.;M;.

PrimateAI

Uncertain

0.68

PROVEAN

Pathogenic

-6.4

D;D;D

REVEL

Uncertain

0.41

Sift

Uncertain

0.0020

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

0.77

.;P;.

Vest4

0.32

MVP

0.62

MPC

0.99

ClinPred

0.23

GERP RS

4.7

Varity_R

0.75

gMVP

0.82

Mutation Taster

=92/8

polymorphism

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