Genetic Variant NM_000778.4:c.511-105T>A (chr1-46935752-A-T) – 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.511-105T>A 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 1,524,684 control chromosomes in the GnomAD database, including 433,753 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 0.65 ( 34632 hom., cov: 33)

Exomes 𝑓: 0.76 ( 399121 hom. )

Consequence

CYP4A11
NM_000778.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.655

Publications

11 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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.98).

BA1

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

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	Effect	Exon Rank	Protein
CYP4A11	NM_000778.4	MANE Select	c.511-105T>A	intron	N/A	NP_000769.2
CYP4A11	NM_001319155.2		c.511-105T>A	intron	N/A	NP_001306084.1
CYP4A11	NM_001363587.2		c.511-105T>A	intron	N/A	NP_001350516.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CYP4A11	ENST00000310638.9	TSL:1 MANE Select	c.511-105T>A	intron	N/A	ENSP00000311095.4
CYP4A11	ENST00000371905.1	TSL:1	c.511-105T>A	intron	N/A	ENSP00000360972.1
CYP4A11	ENST00000465874.5	TSL:2	n.511-105T>A	intron	N/A	ENSP00000476368.1

Frequencies

GnomAD3 genomes

AF:

0.655

AC:

99563

AN:

151954

Hom.:

34631

Cov.:

show subpopulations

Gnomad AFR

AF:

0.414

Gnomad AMI

AF:

0.765

Gnomad AMR

AF:

0.676

Gnomad ASJ

AF:

0.775

Gnomad EAS

AF:

0.514

Gnomad SAS

AF:

0.628

Gnomad FIN

AF:

0.758

Gnomad MID

AF:

0.699

Gnomad NFE

AF:

0.785

Gnomad OTH

AF:

0.683

GnomAD4 exome

AF:

0.757

AC:

1038806

AN:

1372612

Hom.:

399121

AF XY:

0.754

AC XY:

507593

AN XY:

673040

show subpopulations

African (AFR)

AF:

0.387

AC:

12112

AN:

31290

American (AMR)

AF:

0.673

AC:

23412

AN:

34772

Ashkenazi Jewish (ASJ)

AF:

0.779

AC:

16375

AN:

21018

East Asian (EAS)

AF:

0.494

AC:

19131

AN:

38690

South Asian (SAS)

AF:

0.619

AC:

44511

AN:

71908

European-Finnish (FIN)

AF:

0.765

AC:

38326

AN:

50074

Middle Eastern (MID)

AF:

0.723

AC:

3729

AN:

5160

European-Non Finnish (NFE)

AF:

0.790

AC:

839668

AN:

1063144

Other (OTH)

AF:

0.735

AC:

41542

AN:

56556

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.433

Heterozygous variant carriers

10748

21496

32244

42992

53740

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20226

40452

60678

80904

101130

<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:

99574

AN:

152072

Hom.:

34632

Cov.:

AF XY:

0.652

AC XY:

48472

AN XY:

74322

show subpopulations

African (AFR)

AF:

0.413

AC:

17127

AN:

41444

American (AMR)

AF:

0.676

AC:

10321

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.775

AC:

2688

AN:

3470

East Asian (EAS)

AF:

0.513

AC:

2649

AN:

5162

South Asian (SAS)

AF:

0.625

AC:

3008

AN:

4810

European-Finnish (FIN)

AF:

0.758

AC:

8027

AN:

10590

Middle Eastern (MID)

AF:

0.707

AC:

208

AN:

294

European-Non Finnish (NFE)

AF:

0.785

AC:

53393

AN:

68002

Other (OTH)

AF:

0.689

AC:

1458

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1578

3156

4733

6311

7889

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

784

1568

2352

3136

3920

<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:

0.641

Hom.:

2230

Bravo

AF:

0.643

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

0.31

(source)

DANN

Benign

0.46

PhyloP100

-0.66

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over