Genetic Variant CYP4A11:c.1223-24C>G (chr1-46933071-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000778.4(CYP4A11):c.1223-24C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.747 in 1,613,560 control chromosomes in the GnomAD database, including 458,757 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 0.66 ( 34639 hom., cov: 31)

Exomes 𝑓: 0.76 ( 424118 hom. )

Consequence

CYP4A11
NM_000778.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0790

Publications

33 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.78 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP4A11	NM_000778.4 link	c.1223-24C>G		intron_variant	Intron 9 of 11	ENST00000310638.9	NP_000769.2	Q02928-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP4A11	ENST00000310638.9 link	c.1223-24C>G		intron_variant	Intron 9 of 11	1	NM_000778.4	ENSP00000311095.4		Q02928-1
CYP4A11	ENST00000465874.5 link	n.*21-24C>G		intron_variant	Intron 6 of 7	2		ENSP00000476368.1		V9GY41

Frequencies

GnomAD3 genomes

AF:

0.656

AC:

99585

AN:

151902

Hom.:

34638

Cov.:

show subpopulations

Gnomad AFR

AF:

0.415

Gnomad AMI

AF:

0.766

Gnomad AMR

AF:

0.676

Gnomad ASJ

AF:

0.770

Gnomad EAS

AF:

0.521

Gnomad SAS

AF:

0.627

Gnomad FIN

AF:

0.758

Gnomad MID

AF:

0.699

Gnomad NFE

AF:

0.785

Gnomad OTH

AF:

0.685

GnomAD2 exomes

AF:

0.707

AC:

177311

AN:

250836

AF XY:

0.710

show subpopulations

Gnomad AFR exome

AF:

0.405

Gnomad AMR exome

AF:

0.694

Gnomad ASJ exome

AF:

0.776

Gnomad EAS exome

AF:

0.526

Gnomad FIN exome

AF:

0.768

Gnomad NFE exome

AF:

0.785

Gnomad OTH exome

AF:

0.743

GnomAD4 exome

AF:

0.756

AC:

1105572

AN:

1461540

Hom.:

424118

Cov.:

AF XY:

0.754

AC XY:

548091

AN XY:

727042

show subpopulations

African (AFR)

AF:

0.393

AC:

13156

AN:

33472

American (AMR)

AF:

0.690

AC:

30853

AN:

44692

Ashkenazi Jewish (ASJ)

AF:

0.779

AC:

20340

AN:

26112

East Asian (EAS)

AF:

0.498

AC:

19785

AN:

39698

South Asian (SAS)

AF:

0.624

AC:

53753

AN:

86118

European-Finnish (FIN)

AF:

0.767

AC:

40988

AN:

53414

Middle Eastern (MID)

AF:

0.731

AC:

4210

AN:

5760

European-Non Finnish (NFE)

AF:

0.790

AC:

878042

AN:

1111894

Other (OTH)

AF:

0.736

AC:

44445

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

15675

31351

47026

62702

78377

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20522

41044

61566

82088

102610

<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

AF:

0.655

AC:

99596

AN:

152020

Hom.:

34639

Cov.:

AF XY:

0.652

AC XY:

48485

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.414

AC:

17162

AN:

41448

American (AMR)

AF:

0.676

AC:

10331

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.770

AC:

2670

AN:

3468

East Asian (EAS)

AF:

0.520

AC:

2680

AN:

5150

South Asian (SAS)

AF:

0.624

AC:

3000

AN:

4804

European-Finnish (FIN)

AF:

0.758

AC:

8009

AN:

10568

Middle Eastern (MID)

AF:

0.707

AC:

208

AN:

294

European-Non Finnish (NFE)

AF:

0.785

AC:

53381

AN:

67976

Other (OTH)

AF:

0.691

AC:

1458

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1585

3169

4754

6338

7923

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

786

1572

2358

3144

3930

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.728

Hom.:

7602

Bravo

AF:

0.643

Asia WGS

AF:

0.578

AC:

2009

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

7.2

(source)

DANN

Benign

0.59

PhyloP100

-0.079

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over