chr19-15530161-G-A

Variant names:

• chr19-15530161-G-A
• rs1273522
• NM_173483.4:c.367+308G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.338
• Publications: 3 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 -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 VariationId 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.

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.367+308G>A		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.367+308G>A		intron	N/A	ENSP00000269703.1	Q6NT55
	CYP4F22	ENST00000601005.2	TSL:5	c.367+308G>A		intron	N/A	ENSP00000469866.1	Q6NT55
	CYP4F22	ENST00000894419.1		c.367+308G>A		intron	N/A	ENSP00000564478.1

Frequencies

GnomAD3 genomes AF: 0.588 AC: 89291 AN: 151948 Hom.: 27537 Cov.: 32

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.: 32 AF XY: 0.575 AC XY: 42761 AN XY: 74316

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

Alfa AF: 0.583 Hom.: 36412

Bravo AF: 0.609

Asia WGS AF: 0.322 AC: 1126 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.85
DANN	Benign	0.67
PhyloP100		-0.34
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: rs1273522; hg19: chr19-15640972;