Variant rs886041342 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2

The NM_000784.4(CYP27A1):c.11_20delTGGGCTGCGC(p.Leu4fs) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000289 in 1,384,210 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

CYP27A1
NM_000784.4 frameshift

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.60

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 links:

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ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 10 ACMG points.

PVS1

Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 35 pathogenic variants in the truncated region.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP27A1	NM_000784.4 link	c.11_20delTGGGCTGCGC	p.Leu4fs	frameshift_variant	1/9	ENST00000258415.9	NP_000775.1	Q02318

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CYP27A1	ENST00000258415.9 link	c.11_20delTGGGCTGCGC	p.Leu4fs	frameshift_variant	1/9	1	NM_000784.4	ENSP00000258415.4	Q02318
CYP27A1	ENST00000445971.1 link	n.11_20delTGGGCTGCGC		non_coding_transcript_exon_variant	1/5	5		ENSP00000404945.1	F8WD90
CYP27A1	ENST00000466602.1 link	n.20_29delTGGGCTGCGC		non_coding_transcript_exon_variant	1/3	2
CYP27A1	ENST00000494263.5 link	n.445_454delTGGGCTGCGC		non_coding_transcript_exon_variant	1/7	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000289

AC:

AN:

1384210

Hom.:

AF XY:

0.00000586

AC XY:

AN XY:

683160

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000506

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over