Genetic Variant CYP26C1:p.Gly16Ala (chr10-93061310-G-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_183374.3(CYP26C1):c.47G>C(p.Gly16Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000129 in 1,596,588 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.00066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000073 ( 0 hom. )

Consequence

CYP26C1
NM_183374.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.842

Variant links:

Genes affected

CYP26C1 (HGNC:20577): (cytochrome P450 family 26 subfamily C member 1) This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This enzyme is involved in the catabolism of all-trans- and 9-cis-retinoic acid, and thus contributes to the regulation of retinoic acid levels in cells and tissues. This gene is adjacent to a related gene on chromosome 10q23.33. [provided by RefSeq, Jul 2008]

CYP26C1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.006489396).

BP6

Variant 10-93061310-G-C is Benign according to our data. Variant chr10-93061310-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 735624.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP26C1	NM_183374.3 link	c.47G>C	p.Gly16Ala	missense_variant	Exon 1 of 6	ENST00000651965.1	NP_899230.2	Q6V0L0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP26C1	ENST00000651965.1 link	c.47G>C	p.Gly16Ala	missense_variant	Exon 1 of 6		NM_183374.3	ENSP00000498424.1		Q6V0L0
CYP26C1	ENST00000624358.3 link	n.47G>C		non_coding_transcript_exon_variant	Exon 1 of 6	2		ENSP00000485098.1		A0A096LNL5

Frequencies

GnomAD3 genomes

AF:

0.000664

AC:

101

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00232

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000157

AC:

AN:

210270

Hom.:

AF XY:

0.000105

AC XY:

AN XY:

114242

show subpopulations

Gnomad AFR exome

AF:

0.00222

Gnomad AMR exome

AF:

0.0000631

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000221

Gnomad OTH exome

AF:

0.000190

GnomAD4 exome

AF:

0.0000727

AC:

105

AN:

1444318

Hom.:

Cov.:

AF XY:

0.0000586

AC XY:

AN XY:

716706

show subpopulations

Gnomad4 AFR exome

AF:

0.00270

Gnomad4 AMR exome

AF:

0.0000939

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000272

Gnomad4 OTH exome

AF:

0.000117

GnomAD4 genome

AF:

0.000663

AC:

101

AN:

152270

Hom.:

Cov.:

AF XY:

0.000752

AC XY:

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.00231

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000473

Bravo

AF:

0.000790

ESP6500AA

AF:

0.00205

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000159

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Mar 01, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.68

DEOGEN2

Benign

0.026

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.41

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.78

M_CAP

Benign

0.0087

MetaRNN

Benign

0.0065

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

PrimateAI

Uncertain

0.64

PROVEAN

Benign

0.36

REVEL

Benign

0.12

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.024

Vest4

0.31

MVP

0.77

MPC

0.055

ClinPred

0.0054

GERP RS

3.2

Varity_R

0.043

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