chr2-218782001-C-T

Variant names:

• chr2-218782001-C-T
• rs886055628
• ENST00000901552.1:c.-182C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000901552.1(CYP27A1):​c.-182C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000662 in 604,662 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 Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000066 (0 hom.)
• Consequence: CYP27A1 ENST00000901552.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.32
• Publications: 0 publications found

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: Myriad Women’s Health, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), G2P, Orphanet, ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000901552.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP27A1	NM_000784.4	MANE Select	c.-182C>T		upstream_gene	N/A	NP_000775.1	Q02318

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP27A1	ENST00000901552.1		c.-182C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 9	ENSP00000571611.1
	CYP27A1	ENST00000901553.1		c.-182C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 9	ENSP00000571612.1
	CYP27A1	ENST00000901554.1		c.-182C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 9	ENSP00000571613.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000662 AC: 4 AN: 604662 Hom.: 0 Cov.: 8 AF XY: 0.00000651 AC XY: 2 AN XY: 307034

African (AFR) AF: 0.00 AC: 0 AN: 11896

American (AMR) AF: 0.00 AC: 0 AN: 12800

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13180

East Asian (EAS) AF: 0.00 AC: 0 AN: 26528

South Asian (SAS) AF: 0.0000238 AC: 1 AN: 42074

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29192

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2218

European-Non Finnish (NFE) AF: 0.00000458 AC: 2 AN: 436414

Other (OTH) AF: 0.0000329 AC: 1 AN: 30360

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Cholestanol storage disease (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	5.5
DANN	Benign	0.72
PhyloP100		-1.3
PromoterAI		0.0095	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

Other links and lift over

dbSNP: rs886055628; hg19: chr2-219646724;