19-15525387-G-A
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_173483.4(CYP4F22):c.51G>A(p.Thr17=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000388 in 1,614,094 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0023 ( 4 hom., cov: 32)
Exomes 𝑓: 0.00019 ( 1 hom. )
Consequence
CYP4F22
NM_173483.4 synonymous
NM_173483.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -4.41
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BP6
?
Variant 19-15525387-G-A is Benign according to our data. Variant chr19-15525387-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 328423.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-4.41 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00225 (343/152298) while in subpopulation AFR AF= 0.00792 (329/41562). AF 95% confidence interval is 0.00721. There are 4 homozygotes in gnomad4. There are 148 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 3 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CYP4F22 | NM_173483.4 | c.51G>A | p.Thr17= | synonymous_variant | 3/14 | ENST00000269703.8 | |
CYP4F22 | XM_011527692.3 | c.51G>A | p.Thr17= | synonymous_variant | 4/15 | ||
CYP4F22 | XM_011527693.3 | c.51G>A | p.Thr17= | synonymous_variant | 3/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CYP4F22 | ENST00000269703.8 | c.51G>A | p.Thr17= | synonymous_variant | 3/14 | 2 | NM_173483.4 | P1 | |
CYP4F22 | ENST00000601005.2 | c.51G>A | p.Thr17= | synonymous_variant | 1/12 | 5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00222 AC: 338AN: 152178Hom.: 3 Cov.: 32
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GnomAD3 exomes AF: 0.000541 AC: 136AN: 251280Hom.: 1 AF XY: 0.000412 AC XY: 56AN XY: 135838
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GnomAD4 exome AF: 0.000194 AC: 284AN: 1461796Hom.: 1 Cov.: 32 AF XY: 0.000165 AC XY: 120AN XY: 727218
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Autosomal recessive congenital ichthyosis 5 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Oct 03, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at