NM_173483.4:c.582G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_173483.4(CYP4F22):c.582G>A(p.Ala194Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 1,613,962 control chromosomes in the GnomAD database, including 10,055 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.093 ( 744 hom., cov: 31)

Exomes 𝑓: 0.11 ( 9311 hom. )

Consequence

CYP4F22
NM_173483.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.167

Publications

15 publications found

Variant links:

Genes affected

CYP4F22 (HGNC:26820): (cytochrome P450 family 4 subfamily F member 22) 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 gene is part of a cluster of cytochrome P450 genes on chromosome 19 and encodes an enzyme thought to play a role in the 12(R)-lipoxygenase pathway. Mutations in this gene are the cause of ichthyosis lamellar type 3. [provided by RefSeq, Jul 2008]

CYP4F22 Gene-Disease associations (from GenCC):

autosomal recessive congenital ichthyosis 5
Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp, PanelApp Australia, Labcorp Genetics (formerly Invitae)
lamellar ichthyosis
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

CYP4F22 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 19-15537904-G-A is Benign according to our data. Variant chr19-15537904-G-A is described in ClinVar as Benign. ClinVar VariationId is 262835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.167 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP4F22	NM_173483.4 link	c.582G>A	p.Ala194Ala	synonymous_variant	Exon 7 of 14	ENST00000269703.8	NP_775754.2	Q6NT55
CYP4F22	XM_011527692.3 link	c.582G>A	p.Ala194Ala	synonymous_variant	Exon 8 of 15		XP_011525994.1	Q6NT55
CYP4F22	XM_011527693.3 link	c.582G>A	p.Ala194Ala	synonymous_variant	Exon 7 of 14		XP_011525995.1	Q6NT55

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP4F22	ENST00000269703.8 link	c.582G>A	p.Ala194Ala	synonymous_variant	Exon 7 of 14	2	NM_173483.4	ENSP00000269703.1		Q6NT55
CYP4F22	ENST00000601005.2 link	c.582G>A	p.Ala194Ala	synonymous_variant	Exon 5 of 12	5		ENSP00000469866.1		Q6NT55

Frequencies

GnomAD3 genomes

AF:

0.0930

AC:

14137

AN:

152054

Hom.:

742

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0563

Gnomad AMI

AF:

0.0987

Gnomad AMR

AF:

0.0798

Gnomad ASJ

AF:

0.131

Gnomad EAS

AF:

0.0693

Gnomad SAS

AF:

0.0923

Gnomad FIN

AF:

0.102

Gnomad MID

AF:

0.133

Gnomad NFE

AF:

0.116

Gnomad OTH

AF:

0.102

GnomAD2 exomes

AF:

0.0960

AC:

24148

AN:

251458

AF XY:

0.0991

show subpopulations

Gnomad AFR exome

AF:

0.0536

Gnomad AMR exome

AF:

0.0558

Gnomad ASJ exome

AF:

0.133

Gnomad EAS exome

AF:

0.0787

Gnomad FIN exome

AF:

0.104

Gnomad NFE exome

AF:

0.112

Gnomad OTH exome

AF:

0.102

GnomAD4 exome

AF:

0.111

AC:

161862

AN:

1461790

Hom.:

9311

Cov.:

AF XY:

0.110

AC XY:

80312

AN XY:

727190

show subpopulations

African (AFR)

AF:

0.0557

AC:

1866

AN:

33478

American (AMR)

AF:

0.0585

AC:

2617

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.135

AC:

3533

AN:

26136

East Asian (EAS)

AF:

0.0513

AC:

2037

AN:

39700

South Asian (SAS)

AF:

0.0942

AC:

8122

AN:

86256

European-Finnish (FIN)

AF:

0.103

AC:

5491

AN:

53402

Middle Eastern (MID)

AF:

0.132

AC:

752

AN:

5714

European-Non Finnish (NFE)

AF:

0.118

AC:

130688

AN:

1111992

Other (OTH)

AF:

0.112

AC:

6756

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

9468

18936

28405

37873

47341

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4732

9464

14196

18928

23660

<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:

0.0930

AC:

14156

AN:

152172

Hom.:

744

Cov.:

AF XY:

0.0921

AC XY:

6851

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.0564

AC:

2343

AN:

41526

American (AMR)

AF:

0.0797

AC:

1218

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.131

AC:

454

AN:

3466

East Asian (EAS)

AF:

0.0695

AC:

360

AN:

5182

South Asian (SAS)

AF:

0.0934

AC:

450

AN:

4818

European-Finnish (FIN)

AF:

0.102

AC:

1082

AN:

10588

Middle Eastern (MID)

AF:

0.136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.116

AC:

7907

AN:

67998

Other (OTH)

AF:

0.100

AC:

212

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

658

1315

1973

2630

3288

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

158

316

474

632

790

<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:

0.108

Hom.:

2118

Bravo

AF:

0.0889

Asia WGS

AF:

0.0770

AC:

269

AN:

3478

EpiCase

AF:

0.118

EpiControl

AF:

0.119

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Autosomal recessive congenital ichthyosis 5

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

9.7

(source)

DANN

Benign

0.49

PhyloP100

0.17

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over