Variant 10-93074796-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_000783.4(CYP26A1):c.432C>T(p.Phe144Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00174 in 1,605,678 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0015 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0018 ( 4 hom. )

Consequence

CYP26A1
NM_000783.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.24

Variant links:

Genes affected

CYP26A1 (HGNC:2603): (cytochrome P450 family 26 subfamily A 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 endoplasmic reticulum protein acts on retinoids, including all-trans-retinoic acid (RA), with both 4-hydroxylation and 18-hydroxylation activities. This enzyme regulates the cellular level of retinoic acid which is involved in regulation of gene expression in both embryonic and adult tissues. Two alternatively spliced transcript variants of this gene, which encode the distinct isoforms, have been reported. [provided by RefSeq, Jul 2008]

CYP26A1 links:

CYP26A1 (HGNC:):

CYP26A1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant 10-93074796-C-T is Benign according to our data. Variant chr10-93074796-C-T is described in ClinVar as [Benign]. Clinvar id is 775288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.24 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP26A1	NM_000783.4 linkuse as main transcript	c.432C>T	p.Phe144Phe	synonymous_variant	3/7	ENST00000224356.5	NP_000774.2	O43174-1
CYP26A1	NM_057157.2 linkuse as main transcript	c.225C>T	p.Phe75Phe	synonymous_variant	3/7		NP_476498.1	O43174-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP26A1	ENST00000224356.5 linkuse as main transcript	c.432C>T	p.Phe144Phe	synonymous_variant	3/7	1	NM_000783.4	ENSP00000224356.4		O43174-1

Frequencies

GnomAD3 genomes

AF:

0.00145

AC:

221

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000555

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000850

Gnomad ASJ

AF:

0.00634

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00311

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00170

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00190

AC:

456

AN:

240468

Hom.:

AF XY:

0.00217

AC XY:

286

AN XY:

131622

show subpopulations

Gnomad AFR exome

AF:

0.000581

Gnomad AMR exome

AF:

0.00107

Gnomad ASJ exome

AF:

0.00676

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00226

Gnomad FIN exome

AF:

0.00216

Gnomad NFE exome

AF:

0.00205

Gnomad OTH exome

AF:

0.00232

GnomAD4 exome

AF:

0.00177

AC:

2569

AN:

1453348

Hom.:

Cov.:

AF XY:

0.00181

AC XY:

1306

AN XY:

723296

show subpopulations

Gnomad4 AFR exome

AF:

0.000508

Gnomad4 AMR exome

AF:

0.00125

Gnomad4 ASJ exome

AF:

0.00728

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00216

Gnomad4 FIN exome

AF:

0.00155

Gnomad4 NFE exome

AF:

0.00170

Gnomad4 OTH exome

AF:

0.00187

GnomAD4 genome

AF:

0.00148

AC:

226

AN:

152330

Hom.:

Cov.:

AF XY:

0.00169

AC XY:

126

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.000625

Gnomad4 AMR

AF:

0.000849

Gnomad4 ASJ

AF:

0.00634

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.00311

Gnomad4 NFE

AF:

0.00171

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00189

Hom.:

Bravo

AF:

0.00148

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.00245

EpiControl

AF:

0.00332

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Mar 30, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.95

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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