Genetic Variant NM_173483.4:c.367+308G>A (chr19-15530161-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_173483.4(CYP4F22):c.367+308G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.588 in 152,068 control chromosomes in the GnomAD database, including 27,560 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.59 ( 27560 hom., cov: 32)

Consequence

CYP4F22
NM_173483.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.338

Publications

3 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 19-15530161-G-A is Benign according to our data. Variant chr19-15530161-G-A is described in ClinVar as [Benign]. Clinvar id is 1286241.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.738 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CYP4F22	NM_173483.4 link	c.367+308G>A	intron_variant	Intron 4 of 13	ENST00000269703.8	NP_775754.2	Q6NT55
CYP4F22	XM_011527692.3 link	c.367+308G>A	intron_variant	Intron 5 of 14		XP_011525994.1	Q6NT55
CYP4F22	XM_011527693.3 link	c.367+308G>A	intron_variant	Intron 4 of 13		XP_011525995.1	Q6NT55

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP4F22	ENST00000269703.8 link	c.367+308G>A		intron_variant	Intron 4 of 13	2	NM_173483.4	ENSP00000269703.1		Q6NT55
CYP4F22	ENST00000601005.2 link	c.367+308G>A		intron_variant	Intron 2 of 11	5		ENSP00000469866.1		Q6NT55

Frequencies

GnomAD3 genomes

AF:

0.588

AC:

89291

AN:

151948

Hom.:

27537

Cov.:

show subpopulations

Gnomad AFR

AF:

0.744

Gnomad AMI

AF:

0.648

Gnomad AMR

AF:

0.554

Gnomad ASJ

AF:

0.640

Gnomad EAS

AF:

0.238

Gnomad SAS

AF:

0.351

Gnomad FIN

AF:

0.394

Gnomad MID

AF:

0.620

Gnomad NFE

AF:

0.569

Gnomad OTH

AF:

0.613

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.588

AC:

89354

AN:

152068

Hom.:

27560

Cov.:

AF XY:

0.575

AC XY:

42761

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.745

AC:

30923

AN:

41532

American (AMR)

AF:

0.553

AC:

8439

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.640

AC:

2222

AN:

3472

East Asian (EAS)

AF:

0.238

AC:

1229

AN:

5172

South Asian (SAS)

AF:

0.350

AC:

1688

AN:

4820

European-Finnish (FIN)

AF:

0.394

AC:

4151

AN:

10540

Middle Eastern (MID)

AF:

0.622

AC:

183

AN:

294

European-Non Finnish (NFE)

AF:

0.569

AC:

38654

AN:

67956

Other (OTH)

AF:

0.605

AC:

1277

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1796

3593

5389

7186

8982

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

714

1428

2142

2856

3570

<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:

0.583

Hom.:

36412

Bravo

AF:

0.609

Asia WGS

AF:

0.322

AC:

1126

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Nov 11, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.85

(source)

DANN

Benign

0.67

PhyloP100

-0.34

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

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over