Genetic Variant CYP26C1:p.Ala153Ala (chr10-93062749-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6BP7

The NM_183374.3(CYP26C1):c.459G>T(p.Ala153Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000149 in 1,472,442 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 Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00086 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000067 ( 0 hom. )

Consequence

CYP26C1
NM_183374.3 synonymous

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.579

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 -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 10-93062749-G-T is Benign according to our data. Variant chr10-93062749-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 3058564.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.579 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP26C1	NM_183374.3 link	c.459G>T	p.Ala153Ala	synonymous_variant	Exon 3 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.459G>T	p.Ala153Ala	synonymous_variant	Exon 3 of 6		NM_183374.3	ENSP00000498424.1		Q6V0L0
CYP26C1	ENST00000624358.3 link	n.459G>T		non_coding_transcript_exon_variant	Exon 3 of 6	2		ENSP00000485098.1		A0A096LNL5

Frequencies

GnomAD3 genomes

AF:

0.000854

AC:

130

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00304

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000925

AC:

AN:

75692

Hom.:

AF XY:

0.0000472

AC XY:

AN XY:

42362

show subpopulations

Gnomad AFR exome

AF:

0.00155

Gnomad AMR exome

AF:

0.000267

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000674

AC:

AN:

1320128

Hom.:

Cov.:

AF XY:

0.0000370

AC XY:

AN XY:

648298

show subpopulations

Gnomad4 AFR exome

AF:

0.00286

Gnomad4 AMR exome

AF:

0.000234

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:

9.49e-7

Gnomad4 OTH exome

AF:

0.000109

GnomAD4 genome

AF:

0.000860

AC:

131

AN:

152314

Hom.:

Cov.:

AF XY:

0.000899

AC XY:

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.00305

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000847

Hom.:

Bravo

AF:

0.00110

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CYP26C1-related disorder

Benign:1

Apr 10, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

8.1

DANN

Benign

0.95

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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