Genetic Variant CYP27A1:n.78dupC (chr2-218781824-A-AC) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The ENST00000494263.5(CYP27A1):n.78dupC variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 1.0 ( 76157 hom., cov: 0)

Exomes 𝑓: 1.0 ( 45998 hom. )

Consequence

CYP27A1
ENST00000494263.5 non_coding_transcript_exon

Scores

Not classified

Clinical Significance

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

Conservation

PhyloP100: -1.08

Publications

2 publications found

Variant links:

Genes affected

CYP27A1 (HGNC:2605): (cytochrome P450 family 27 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 mitochondrial protein oxidizes cholesterol intermediates as part of the bile synthesis pathway. Since the conversion of cholesterol to bile acids is the major route for removing cholesterol from the body, this protein is important for overall cholesterol homeostasis. Mutations in this gene cause cerebrotendinous xanthomatosis, a rare autosomal recessive lipid storage disease. [provided by RefSeq, Jul 2008]

CYP27A1 Gene-Disease associations (from GenCC):

cerebrotendinous xanthomatosis
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Myriad Women’s Health, Genomics England PanelApp, G2P

CYP27A1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP6

Variant 2-218781824-A-AC is Benign according to our data. Variant chr2-218781824-A-AC is described in ClinVar as [Benign]. Clinvar id is 334362.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.994 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP27A1	ENST00000494263.5 link	n.78dupC		non_coding_transcript_exon_variant	Exon 1 of 7	2

Frequencies

GnomAD3 genomes

AF:

1.00

AC:

152196

AN:

152196

Hom.:

76098

Cov.:

show subpopulations

Gnomad AFR

AF:

1.00

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

1.00

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

1.00

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

1.00

Gnomad NFE

AF:

1.00

Gnomad OTH

AF:

1.00

GnomAD4 exome

AF:

1.00

AC:

92002

AN:

92008

Hom.:

45998

Cov.:

AF XY:

1.00

AC XY:

46781

AN XY:

46784

show subpopulations

African (AFR)

AF:

1.00

AC:

2482

AN:

2482

American (AMR)

AF:

1.00

AC:

2492

AN:

2492

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

3287

AN:

3288

East Asian (EAS)

AF:

1.00

AC:

5626

AN:

5626

South Asian (SAS)

AF:

1.00

AC:

6116

AN:

6116

European-Finnish (FIN)

AF:

1.00

AC:

5857

AN:

5858

Middle Eastern (MID)

AF:

1.00

AC:

498

AN:

498

European-Non Finnish (NFE)

AF:

1.00

AC:

59510

AN:

59514

Other (OTH)

AF:

1.00

AC:

6134

AN:

6134

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.808

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

1.00

AC:

152314

AN:

152314

Hom.:

76157

Cov.:

AF XY:

1.00

AC XY:

74468

AN XY:

74468

show subpopulations

African (AFR)

AF:

1.00

AC:

41582

AN:

41582

American (AMR)

AF:

1.00

AC:

15308

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

3472

AN:

3472

East Asian (EAS)

AF:

1.00

AC:

5168

AN:

5168

South Asian (SAS)

AF:

1.00

AC:

4824

AN:

4824

European-Finnish (FIN)

AF:

1.00

AC:

10614

AN:

10614

Middle Eastern (MID)

AF:

1.00

AC:

294

AN:

294

European-Non Finnish (NFE)

AF:

1.00

AC:

68024

AN:

68024

Other (OTH)

AF:

1.00

AC:

2116

AN:

2116

Alfa

AF:

0.997

Hom.:

8125

Asia WGS

AF:

1.00

AC:

3478

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Cholestanol storage disease

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Oct 18, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-1.1

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

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chr2-218781824-A-AC

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over