rs13013510

Variant names:

• chr2-218802504-A-G
• rs13013510
• NM_000784.4:c.256-7073A>G

Your query was ambiguous. Multiple possible variants found:

• chr2-218802504-A-G
• chr2-218802504-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.256-7073A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.517 in 151,942 control chromosomes in the GnomAD database, including 21,043 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 0.52 (21043 hom., cov: 31)
• Consequence: CYP27A1 NM_000784.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.711
• Publications: 11 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.609 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP27A1	NM_000784.4	c.256-7073A>G		intron_variant	Intron 1 of 8	ENST00000258415.9	NP_000775.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP27A1	ENST00000258415.9	c.256-7073A>G		intron_variant	Intron 1 of 8	1	NM_000784.4	ENSP00000258415.4

Frequencies

GnomAD3 genomes AF: 0.517 AC: 78437 AN: 151824 Hom.: 21021 Cov.: 31

Gnomad AFR AF: 0.615

Gnomad AMI AF: 0.415

Gnomad AMR AF: 0.458

Gnomad ASJ AF: 0.440

Gnomad EAS AF: 0.165

Gnomad SAS AF: 0.363

Gnomad FIN AF: 0.562

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.507

Gnomad OTH AF: 0.500

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

GnomAD4 genome AF: 0.517 AC: 78507 AN: 151942 Hom.: 21043 Cov.: 31 AF XY: 0.512 AC XY: 38019 AN XY: 74272

African (AFR) AF: 0.615 AC: 25469 AN: 41406

American (AMR) AF: 0.457 AC: 6980 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.440 AC: 1526 AN: 3466

East Asian (EAS) AF: 0.166 AC: 861 AN: 5182

South Asian (SAS) AF: 0.363 AC: 1748 AN: 4818

European-Finnish (FIN) AF: 0.562 AC: 5922 AN: 10540

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.507 AC: 34451 AN: 67958

Other (OTH) AF: 0.500 AC: 1052 AN: 2106

Alfa AF: 0.502 Hom.: 14519

Bravo AF: 0.515

Asia WGS AF: 0.303 AC: 1054 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.6
DANN	Benign	0.64
PhyloP100		0.71
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs13013510; hg19: chr2-219667227;