rs7566656

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP27A1	NM_000784.4	c.256-9781A>G		intron_variant		ENST00000258415.9	NP_000775.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP27A1	ENST00000258415.9	c.256-9781A>G		intron_variant		1	NM_000784.4	ENSP00000258415	P1
	ENST00000652549.1	n.849T>C		non_coding_transcript_exon_variant	2/2

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

Gnomad4 AFR AF: 0.462

Gnomad4 AMR AF: 0.436

Gnomad4 ASJ AF: 0.437

Gnomad4 EAS AF: 0.165

Gnomad4 SAS AF: 0.361

Gnomad4 FIN AF: 0.561

Gnomad4 NFE AF: 0.505

Gnomad4 OTH AF: 0.463

Alfa AF: 0.489 Hom.: 23597

Bravo AF: 0.463

Asia WGS AF: 0.288 AC: 1005 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	8.9
DANN	Benign	0.78

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

LitVar

Other links and lift over

dbSNP: rs7566656; hg19: chr2-219664519;