19-15525307-A-G

Variant names:

• chr19-15525307-A-G
• rs73929924
• NM_173483.4:c.-1-29A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_173483.4(CYP4F22):​c.-1-29A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0149 in 1,606,594 control chromosomes in the GnomAD database, including 388 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.030 (153 hom., cov: 32)
  • Exomes 𝑓: 0.013 (235 hom.)
• Consequence: CYP4F22 NM_173483.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.116
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 19-15525307-A-G is Benign according to our data. Variant chr19-15525307-A-G is described in ClinVar as Benign. ClinVar VariationId is 1237700.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0761 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.-1-29A>G		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.-1-29A>G		intron	N/A	ENSP00000269703.1	Q6NT55
	CYP4F22	ENST00000894419.1		c.-1-29A>G		intron	N/A	ENSP00000564478.1
	CYP4F22	ENST00000894420.1		c.-1-29A>G		intron	N/A	ENSP00000564479.1

Frequencies

GnomAD3 genomes AF: 0.0295 AC: 4486 AN: 152108 Hom.: 154 Cov.: 32

Gnomad AFR AF: 0.0783

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0138

Gnomad ASJ AF: 0.0115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00787

Gnomad FIN AF: 0.000660

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0132

Gnomad OTH AF: 0.0211

GnomAD2 exomes AF: 0.0132 AC: 3233 AN: 244912 AF XY: 0.0121

Gnomad AFR exome AF: 0.0754

Gnomad AMR exome AF: 0.00758

Gnomad ASJ exome AF: 0.0109

Gnomad EAS exome AF: 0.000165

Gnomad FIN exome AF: 0.000897

Gnomad NFE exome AF: 0.0121

Gnomad OTH exome AF: 0.0114

GnomAD4 exome AF: 0.0133 AC: 19394 AN: 1454368 Hom.: 235 Cov.: 31 AF XY: 0.0130 AC XY: 9426 AN XY: 723716

African (AFR) AF: 0.0800 AC: 2671 AN: 33374

American (AMR) AF: 0.00900 AC: 400 AN: 44456

Ashkenazi Jewish (ASJ) AF: 0.0104 AC: 271 AN: 26076

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39610

South Asian (SAS) AF: 0.00713 AC: 613 AN: 85992

European-Finnish (FIN) AF: 0.000938 AC: 47 AN: 50090

Middle Eastern (MID) AF: 0.0169 AC: 97 AN: 5750

European-Non Finnish (NFE) AF: 0.0130 AC: 14365 AN: 1108808

Other (OTH) AF: 0.0154 AC: 925 AN: 60212

GnomAD4 genome AF: 0.0295 AC: 4493 AN: 152226 Hom.: 153 Cov.: 32 AF XY: 0.0282 AC XY: 2098 AN XY: 74436

African (AFR) AF: 0.0783 AC: 3252 AN: 41528

American (AMR) AF: 0.0137 AC: 210 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0115 AC: 40 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00767 AC: 37 AN: 4824

European-Finnish (FIN) AF: 0.000660 AC: 7 AN: 10614

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0132 AC: 897 AN: 67994

Other (OTH) AF: 0.0209 AC: 44 AN: 2110

Alfa AF: 0.0181 Hom.: 14

Bravo AF: 0.0320

Asia WGS AF: 0.0110 AC: 37 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.3
DANN	Benign	0.67
PhyloP100		0.12
PromoterAI		0.00060	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		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: rs73929924; hg19: chr19-15636118;