Variant rs4900442 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006668.2(CYP46A1):c.282+43C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 1,594,892 control chromosomes in the GnomAD database, including 172,128 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 0.43 ( 14655 hom., cov: 32)

Exomes 𝑓: 0.47 ( 157473 hom. )

Consequence

CYP46A1
NM_006668.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.597

Variant links:

Genes affected

CYP46A1 (HGNC:2641): (cytochrome P450 family 46 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 endoplasmic reticulum protein is expressed in the brain, where it converts cholesterol to 24S-hydroxycholesterol. While cholesterol cannot pass the blood-brain barrier, 24S-hydroxycholesterol can be secreted in the brain into the circulation to be returned to the liver for catabolism. [provided by RefSeq, Jul 2008]

CYP46A1 links:

ENSG00000258672 (HGNC:):

ENSG00000258672 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.493 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
CYP46A1	NM_006668.2 link	c.282+43C>T	intron_variant	ENST00000261835.8	NP_006659.1	Q9Y6A2-1
CYP46A1	XM_011536364.2 link	c.282+43C>T	intron_variant		XP_011534666.1
CYP46A1	XM_017020933.3 link	c.125+43C>T	intron_variant		XP_016876422.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
CYP46A1	ENST00000261835.8 link	c.282+43C>T	intron_variant	1	NM_006668.2	ENSP00000261835.3	Q9Y6A2-1
CYP46A1	ENST00000554611.5 link	n.282+43C>T	intron_variant	1		ENSP00000451069.1	G3V366
CYP46A1	ENST00000380228.6 link	c.-10+43C>T	intron_variant	2		ENSP00000369577.3	Q9Y6A2-2
ENSG00000258672	ENST00000555875.1 link	n.91-57G>A	intron_variant	3

Frequencies

GnomAD3 genomes

AF:

0.433

AC:

65679

AN:

151802

Hom.:

14642

Cov.:

show subpopulations

Gnomad AFR

AF:

0.333

Gnomad AMI

AF:

0.513

Gnomad AMR

AF:

0.502

Gnomad ASJ

AF:

0.458

Gnomad EAS

AF:

0.494

Gnomad SAS

AF:

0.502

Gnomad FIN

AF:

0.446

Gnomad MID

AF:

0.487

Gnomad NFE

AF:

0.463

Gnomad OTH

AF:

0.428

GnomAD3 exomes

AF:

0.474

AC:

118829

AN:

250456

Hom.:

28731

AF XY:

0.474

AC XY:

64091

AN XY:

135338

show subpopulations

Gnomad AFR exome

AF:

0.323

Gnomad AMR exome

AF:

0.575

Gnomad ASJ exome

AF:

0.462

Gnomad EAS exome

AF:

0.495

Gnomad SAS exome

AF:

0.492

Gnomad FIN exome

AF:

0.455

Gnomad NFE exome

AF:

0.463

Gnomad OTH exome

AF:

0.466

GnomAD4 exome

AF:

0.466

AC:

672386

AN:

1442972

Hom.:

157473

Cov.:

AF XY:

0.466

AC XY:

335025

AN XY:

718946

show subpopulations

Gnomad4 AFR exome

AF:

0.317

Gnomad4 AMR exome

AF:

0.568

Gnomad4 ASJ exome

AF:

0.459

Gnomad4 EAS exome

AF:

0.519

Gnomad4 SAS exome

AF:

0.493

Gnomad4 FIN exome

AF:

0.456

Gnomad4 NFE exome

AF:

0.464

Gnomad4 OTH exome

AF:

0.458

GnomAD4 genome

AF:

0.433

AC:

65728

AN:

151920

Hom.:

14655

Cov.:

AF XY:

0.432

AC XY:

32108

AN XY:

74256

show subpopulations

Gnomad4 AFR

AF:

0.333

Gnomad4 AMR

AF:

0.502

Gnomad4 ASJ

AF:

0.458

Gnomad4 EAS

AF:

0.494

Gnomad4 SAS

AF:

0.502

Gnomad4 FIN

AF:

0.446

Gnomad4 NFE

AF:

0.463

Gnomad4 OTH

AF:

0.434

Alfa

AF:

0.447

Hom.:

5960

Bravo

AF:

0.432

Asia WGS

AF:

0.500

AC:

1741

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.1

DANN

Benign

0.75

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over