rs1273522

chr19-15530161-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP4F22	NM_173483.4	c.367+308G>A		intron_variant		ENST00000269703.8
CYP4F22	XM_011527692.3	c.367+308G>A		intron_variant
CYP4F22	XM_011527693.3	c.367+308G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP4F22	ENST00000269703.8	c.367+308G>A		intron_variant		2	NM_173483.4	P1
CYP4F22	ENST00000601005.2	c.367+308G>A		intron_variant		5		P1

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

Gnomad4 AFR AF: 0.745

Gnomad4 AMR AF: 0.553

Gnomad4 ASJ AF: 0.640

Gnomad4 EAS AF: 0.238

Gnomad4 SAS AF: 0.350

Gnomad4 FIN AF: 0.394

Gnomad4 NFE AF: 0.569

Gnomad4 OTH AF: 0.605

Alfa AF: 0.578 Hom.: 28513

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

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.85
Dann	Benign	0.67

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

LitVar

Other links and lift over

dbSNP: rs1273522; hg19: chr19-15640972;