Genetic Variant CYP4A11:p.Pro512Leu (chr1-46930140-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000778.4(CYP4A11):c.1535C>T(p.Pro512Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,280 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P512R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CYP4A11
NM_000778.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.899

Publications

1 publications found

Variant links:

Genes affected

CYP4A11 (HGNC:2642): (cytochrome P450 family 4 subfamily A member 11) 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 and hydroxylates medium-chain fatty acids such as laurate and myristate. Multiple transcript variants have been found for this gene. [provided by RefSeq, Jan 2016]

CYP4A11 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18054086).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000778.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CYP4A11	NM_000778.4	MANE Select	c.1535C>T	p.Pro512Leu	missense	Exon 12 of 12	NP_000769.2	Q02928-1
CYP4A11	NM_001319155.2		c.1439C>T	p.Pro480Leu	missense	Exon 12 of 12	NP_001306084.1
CYP4A11	NM_001363587.2		c.1241C>T	p.Pro414Leu	missense	Exon 10 of 10	NP_001350516.1	V9GZ77

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CYP4A11	ENST00000310638.9	TSL:1 MANE Select	c.1535C>T	p.Pro512Leu	missense	Exon 12 of 12	ENSP00000311095.4	Q02928-1
CYP4A11	ENST00000909039.1		c.1646C>T	p.Pro549Leu	missense	Exon 12 of 12	ENSP00000579098.1
CYP4A11	ENST00000909036.1		c.1559C>T	p.Pro520Leu	missense	Exon 12 of 12	ENSP00000579095.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461280

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726926

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33472

American (AMR)

AF:

0.00

AC:

AN:

44674

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26084

East Asian (EAS)

AF:

0.00

AC:

AN:

39688

South Asian (SAS)

AF:

0.00

AC:

AN:

86158

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53396

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111686

Other (OTH)

AF:

0.0000166

AC:

AN:

60360

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000225

Hom.:

Bravo

AF:

0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.073

BayesDel_noAF

Benign

-0.34

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.13

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.57

FATHMM_MKL

Benign

0.066

LIST_S2

Benign

0.64

M_CAP

Benign

0.014

MetaRNN

Benign

0.18

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.12

PhyloP100

0.90

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.61

REVEL

Benign

0.19

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.044

Polyphen

1.0

Vest4

0.11

MutPred

0.31

Loss of disorder (P = 0.0227)

MVP

0.77

MPC

0.088

ClinPred

0.25

GERP RS

2.3

Varity_R

0.045

gMVP

0.40

Mutation Taster

=95/5

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over