Variant 1-46799094-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001099772.2(CYP4B1):c.13T>A(p.Phe5Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000514 in 1,614,046 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0029 ( 3 hom., cov: 33)

Exomes 𝑓: 0.00027 ( 1 hom. )

Consequence

CYP4B1
NM_001099772.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.560

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0052030087).

BP6

Variant 1-46799094-T-A is Benign according to our data. Variant chr1-46799094-T-A is described in ClinVar as [Benign]. Clinvar id is 727574.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP4B1	NM_001099772.2 linkuse as main transcript	c.13T>A	p.Phe5Ile	missense_variant	1/12	ENST00000371923.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP4B1	ENST00000371923.9 linkuse as main transcript	c.13T>A	p.Phe5Ile	missense_variant	1/12	1	NM_001099772.2	A1	P13584-2

Frequencies

GnomAD3 genomes

AF:

0.00283

AC:

431

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00982

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00118

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.000698

AC:

175

AN:

250696

Hom.:

AF XY:

0.000554

AC XY:

AN XY:

135476

show subpopulations

Gnomad AFR exome

AF:

0.00942

Gnomad AMR exome

AF:

0.000521

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000328

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000491

GnomAD4 exome

AF:

0.000270

AC:

395

AN:

1461714

Hom.:

Cov.:

AF XY:

0.000264

AC XY:

192

AN XY:

727132

show subpopulations

Gnomad4 AFR exome

AF:

0.00947

Gnomad4 AMR exome

AF:

0.000581

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000104

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.000563

GnomAD4 genome

AF:

0.00286

AC:

435

AN:

152332

Hom.:

Cov.:

AF XY:

0.00273

AC XY:

203

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.00988

Gnomad4 AMR

AF:

0.00118

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00236

Alfa

AF:

0.000436

Hom.:

Bravo

AF:

0.00310

ESP6500AA

AF:

0.00976

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000889

AC:

108

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.41

CADD

Benign

7.4

DANN

Benign

0.94

DEOGEN2

Benign

0.010

T;.;T;.;T

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.063

LIST_S2

Benign

0.52

T;T;T;T;.

M_CAP

Benign

0.017

MetaRNN

Benign

0.0052

T;T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.4

.;L;L;.;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.81

.;N;N;N;.

REVEL

Benign

0.17

Sift

Benign

0.26

.;T;T;T;.

Sift4G

Benign

0.38

.;T;T;T;T

Polyphen

0.082, 0.049

.;B;B;B;.

Vest4

0.24, 0.24, 0.33, 0.30

MVP

0.57

MPC

0.12

ClinPred

0.0029

GERP RS

4.8

Varity_R

0.098

gMVP

0.44

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over