rs11677711

Positions:

• chr2-218804652-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000784.4(CYP27A1):​c.256-4925T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0306 in 152,366 control chromosomes in the GnomAD database, including 123 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 0.031 (123 hom., cov: 33)
• Consequence: CYP27A1 NM_000784.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.812

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0306 (4665/152366) while in subpopulation NFE AF= 0.0454 (3088/68038). AF 95% confidence interval is 0.0441. There are 123 homozygotes in gnomad4. There are 2238 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 123 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP27A1	NM_000784.4	c.256-4925T>G		intron_variant		ENST00000258415.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP27A1	ENST00000258415.9	c.256-4925T>G		intron_variant		1	NM_000784.4	P1
CYP27A1	ENST00000445971.1	c.256-7570T>G		intron_variant, NMD_transcript_variant		5
CYP27A1	ENST00000466602.1	n.265-7570T>G		intron_variant, non_coding_transcript_variant		2
CYP27A1	ENST00000494263.5	n.690-4925T>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0306 AC: 4664 AN: 152248 Hom.: 123 Cov.: 33

Gnomad AFR AF: 0.00755

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.0245

Gnomad ASJ AF: 0.0190

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00414

Gnomad FIN AF: 0.0562

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0454

Gnomad OTH AF: 0.0234

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

GnomAD4 genome AF: 0.0306 AC: 4665 AN: 152366 Hom.: 123 Cov.: 33 AF XY: 0.0300 AC XY: 2238 AN XY: 74514

Gnomad4 AFR AF: 0.00753

Gnomad4 AMR AF: 0.0244

Gnomad4 ASJ AF: 0.0190

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00435

Gnomad4 FIN AF: 0.0562

Gnomad4 NFE AF: 0.0454

Gnomad4 OTH AF: 0.0232

Alfa AF: 0.0392 Hom.: 185

Bravo AF: 0.0285

Asia WGS AF: 0.00491 AC: 17 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	8.2
DANN	Benign	0.71

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: rs11677711; hg19: chr2-219669375;