rs7566656

Variant names:

• chr2-218799796-A-G
• rs7566656
• NM_000784.4:c.256-9781A>G

Your query was ambiguous. Multiple possible variants found:

• chr2-218799796-A-G
• chr2-218799796-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000784.4(CYP27A1):​c.256-9781A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.471 in 151,544 control chromosomes in the GnomAD database, including 17,310 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.47 (17310 hom., cov: 29)
• Consequence: CYP27A1 NM_000784.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0500
• Publications: 14 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: Orphanet, Labcorp Genetics (formerly Invitae), Myriad Women’s Health, Genomics England PanelApp, G2P

ENSG00000286154 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.501 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000784.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP27A1	NM_000784.4	MANE Select	c.256-9781A>G		intron	N/A	NP_000775.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP27A1	ENST00000258415.9	TSL:1 MANE Select	c.256-9781A>G		intron	N/A	ENSP00000258415.4
	CYP27A1	ENST00000901552.1		c.256-9781A>G		intron	N/A	ENSP00000571611.1
	CYP27A1	ENST00000901553.1		c.256-9781A>G		intron	N/A	ENSP00000571612.1

Frequencies

GnomAD3 genomes AF: 0.471 AC: 71379 AN: 151426 Hom.: 17304 Cov.: 29

Gnomad AFR AF: 0.462

Gnomad AMI AF: 0.417

Gnomad AMR AF: 0.437

Gnomad ASJ AF: 0.437

Gnomad EAS AF: 0.165

Gnomad SAS AF: 0.360

Gnomad FIN AF: 0.561

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.505

Gnomad OTH AF: 0.463

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.471 AC: 71417 AN: 151544 Hom.: 17310 Cov.: 29 AF XY: 0.468 AC XY: 34670 AN XY: 74016

African (AFR) AF: 0.462 AC: 19039 AN: 41254

American (AMR) AF: 0.436 AC: 6630 AN: 15210

Ashkenazi Jewish (ASJ) AF: 0.437 AC: 1513 AN: 3460

East Asian (EAS) AF: 0.165 AC: 850 AN: 5136

South Asian (SAS) AF: 0.361 AC: 1726 AN: 4784

European-Finnish (FIN) AF: 0.561 AC: 5901 AN: 10510

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.505 AC: 34290 AN: 67880

Other (OTH) AF: 0.463 AC: 975 AN: 2104

Alfa AF: 0.488 Hom.: 29961

Bravo AF: 0.463

Asia WGS AF: 0.288 AC: 1005 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	8.9
DANN	Benign	0.78
PhyloP100		0.050
Mutation Taster		=100/0	polymorphism (auto)

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: rs7566656; hg19: chr2-219664519;