Genetic Variant CYP4A11:c.1222+121A>G (chr1-46933825-T-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.1222+121A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 1,445,466 control chromosomes in the GnomAD database, including 16,746 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 0.16 ( 2027 hom., cov: 30)

Exomes 𝑓: 0.14 ( 14719 hom. )

Consequence

CYP4A11
NM_000778.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.47

Publications

10 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=-0.92).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.268 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP4A11	NM_000778.4 link	c.1222+121A>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.1222+121A>G		intron_variant	Intron 9 of 11	1	NM_000778.4	ENSP00000311095.4		Q02928-1
CYP4A11	ENST00000465874.5 link	n.*20+121A>G		intron_variant	Intron 6 of 7	2		ENSP00000476368.1		V9GY41

Frequencies

GnomAD3 genomes

AF:

0.158

AC:

23983

AN:

152042

Hom.:

2023

Cov.:

show subpopulations

Gnomad AFR

AF:

0.202

Gnomad AMI

AF:

0.190

Gnomad AMR

AF:

0.136

Gnomad ASJ

AF:

0.121

Gnomad EAS

AF:

0.225

Gnomad SAS

AF:

0.279

Gnomad FIN

AF:

0.117

Gnomad MID

AF:

0.174

Gnomad NFE

AF:

0.130

Gnomad OTH

AF:

0.149

GnomAD4 exome

AF:

0.143

AC:

185325

AN:

1293306

Hom.:

14719

AF XY:

0.147

AC XY:

92392

AN XY:

630336

show subpopulations

African (AFR)

AF:

0.210

AC:

6005

AN:

28620

American (AMR)

AF:

0.140

AC:

3217

AN:

23026

Ashkenazi Jewish (ASJ)

AF:

0.118

AC:

2268

AN:

19274

East Asian (EAS)

AF:

0.223

AC:

8082

AN:

36222

South Asian (SAS)

AF:

0.285

AC:

18344

AN:

64274

European-Finnish (FIN)

AF:

0.116

AC:

5462

AN:

47024

Middle Eastern (MID)

AF:

0.165

AC:

689

AN:

4172

European-Non Finnish (NFE)

AF:

0.131

AC:

133244

AN:

1017188

Other (OTH)

AF:

0.150

AC:

8014

AN:

53506

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

7907

15813

23720

31626

39533

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5196

10392

15588

20784

25980

<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:

0.158

AC:

24005

AN:

152160

Hom.:

2027

Cov.:

AF XY:

0.160

AC XY:

11866

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.202

AC:

8363

AN:

41486

American (AMR)

AF:

0.136

AC:

2078

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.121

AC:

420

AN:

3472

East Asian (EAS)

AF:

0.225

AC:

1161

AN:

5162

South Asian (SAS)

AF:

0.281

AC:

1353

AN:

4816

European-Finnish (FIN)

AF:

0.117

AC:

1243

AN:

10598

Middle Eastern (MID)

AF:

0.160

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.130

AC:

8856

AN:

68016

Other (OTH)

AF:

0.147

AC:

311

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1046

2092

3139

4185

5231

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

274

548

822

1096

1370

<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:

0.139

Hom.:

1710

Bravo

AF:

0.157

Asia WGS

AF:

0.237

AC:

822

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.041

(source)

DANN

Benign

0.47

PhyloP100

-1.5

Mutation Taster

=100/0

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over