Variant 1-46810914-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001099772.2(CYP4B1):c.287A>G(p.Glu96Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,864 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

CYP4B1
NM_001099772.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.06

Variant links:

Genes affected

CYP4B1 (HGNC:2644): (cytochrome P450 family 4 subfamily B 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 protein localizes to the endoplasmic reticulum. In rodents, the homologous protein has been shown to metabolize certain carcinogens; however, the specific function of the human protein has not been determined. Multiple transcript variants have been found for this gene. [provided by RefSeq, Jan 2016]

CYP4B1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP4B1	NM_001099772.2 linkuse as main transcript	c.287A>G	p.Glu96Gly	missense_variant	2/12	ENST00000371923.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP4B1	ENST00000371923.9 linkuse as main transcript	c.287A>G	p.Glu96Gly	missense_variant	2/12	1	NM_001099772.2	A1	P13584-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251124

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135744

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000463

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461864

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000374

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 10, 2023

The c.287A>G (p.E96G) alteration is located in exon 2 (coding exon 2) of the CYP4B1 gene. This alteration results from a A to G substitution at nucleotide position 287, causing the glutamic acid (E) at amino acid position 96 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.38

BayesDel_addAF

Uncertain

0.023

BayesDel_noAF

Benign

-0.19

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.064

T;.;T;.;T

Eigen

Benign

0.12

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Benign

0.83

T;D;D;D;.

M_CAP

Benign

0.055

MetaRNN

Uncertain

0.55

D;D;D;D;D

MetaSVM

Benign

-0.56

MutationAssessor

Benign

1.3

.;L;L;.;.

MutationTaster

Benign

0.99

D;D;D

PrimateAI

Benign

0.39

PROVEAN

Uncertain

-3.1

.;D;D;D;.

REVEL

Uncertain

0.39

Sift

Uncertain

0.021

.;D;D;D;.

Sift4G

Benign

0.20

.;T;T;T;T

Polyphen

0.31, 0.36, 0.86

.;B;B;P;.

Vest4

0.40, 0.39, 0.30, 0.39

MutPred

0.56

Loss of ubiquitination at K101 (P = 0.1037);Loss of ubiquitination at K101 (P = 0.1037);Loss of ubiquitination at K101 (P = 0.1037);Loss of ubiquitination at K101 (P = 0.1037);Loss of ubiquitination at K101 (P = 0.1037);

MVP

0.80

MPC

0.23

ClinPred

0.88

GERP RS

5.6

Varity_R

0.23

gMVP

0.44

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over