19-15534809-C-T

Variant names:

• chr19-15534809-C-T
• rs892143
• NM_173483.4:c.368-2552C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173483.4(CYP4F22):​c.368-2552C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.872 in 151,934 control chromosomes in the GnomAD database, including 58,019 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 0.87 (58019 hom., cov: 30)
• Consequence: CYP4F22 NM_173483.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.27
• Publications: 1 publications found

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, Labcorp Genetics (formerly Invitae)
• lamellar ichthyosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.938 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173483.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP4F22	NM_173483.4	MANE Select	c.368-2552C>T		intron	N/A	NP_775754.2	Q6NT55

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP4F22	ENST00000269703.8	TSL:2 MANE Select	c.368-2552C>T		intron	N/A	ENSP00000269703.1	Q6NT55
	CYP4F22	ENST00000601005.2	TSL:5	c.368-2552C>T		intron	N/A	ENSP00000469866.1	Q6NT55
	CYP4F22	ENST00000894419.1		c.368-2552C>T		intron	N/A	ENSP00000564478.1

Frequencies

GnomAD3 genomes AF: 0.872 AC: 132406 AN: 151816 Hom.: 57966 Cov.: 30

Gnomad AFR AF: 0.946

Gnomad AMI AF: 0.951

Gnomad AMR AF: 0.885

Gnomad ASJ AF: 0.921

Gnomad EAS AF: 0.889

Gnomad SAS AF: 0.807

Gnomad FIN AF: 0.804

Gnomad MID AF: 0.924

Gnomad NFE AF: 0.834

Gnomad OTH AF: 0.889

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

GnomAD4 genome AF: 0.872 AC: 132520 AN: 151934 Hom.: 58019 Cov.: 30 AF XY: 0.872 AC XY: 64713 AN XY: 74248

African (AFR) AF: 0.946 AC: 39204 AN: 41434

American (AMR) AF: 0.885 AC: 13495 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.921 AC: 3193 AN: 3468

East Asian (EAS) AF: 0.889 AC: 4575 AN: 5144

South Asian (SAS) AF: 0.809 AC: 3894 AN: 4816

European-Finnish (FIN) AF: 0.804 AC: 8477 AN: 10542

Middle Eastern (MID) AF: 0.925 AC: 270 AN: 292

European-Non Finnish (NFE) AF: 0.834 AC: 56666 AN: 67964

Other (OTH) AF: 0.890 AC: 1879 AN: 2112

Alfa AF: 0.852 Hom.: 89791

Bravo AF: 0.883

Asia WGS AF: 0.839 AC: 2919 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	11
DANN	Benign	0.61
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs892143; hg19: chr19-15645620;