chr19-15525513-C-T

Variant names:

• chr19-15525513-C-T
• rs118091316
• NM_173483.4:c.177C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_173483.4(CYP4F22):​c.177C>T​(p.Phe59Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0102 in 1,612,182 control chromosomes in the GnomAD database, including 109 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0083 (10 hom., cov: 32)
  • Exomes 𝑓: 0.010 (99 hom.)
• Consequence: CYP4F22 NM_173483.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 2.06
• Publications: 9 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BP6: Variant 19-15525513-C-T is Benign according to our data. Variant chr19-15525513-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 719452.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.06 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00831 (1265/152310) while in subpopulation NFE AF = 0.012 (813/68012). AF 95% confidence interval is 0.0113. There are 10 homozygotes in GnomAd4. There are 652 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 10 AR gene

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.177C>T	p.Phe59Phe	synonymous	Exon 3 of 14	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.177C>T	p.Phe59Phe	synonymous	Exon 3 of 14	ENSP00000269703.1	Q6NT55
	CYP4F22	ENST00000601005.2	TSL:5	c.177C>T	p.Phe59Phe	synonymous	Exon 1 of 12	ENSP00000469866.1	Q6NT55
	CYP4F22	ENST00000894419.1		c.177C>T	p.Phe59Phe	synonymous	Exon 4 of 15	ENSP00000564478.1

Frequencies

GnomAD3 genomes AF: 0.00833 AC: 1267 AN: 152192 Hom.: 10 Cov.: 32

Gnomad AFR AF: 0.00200

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00682

Gnomad FIN AF: 0.0271

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0120

Gnomad OTH AF: 0.00430

GnomAD2 exomes AF: 0.00840 AC: 2097 AN: 249736 AF XY: 0.00858

Gnomad AFR exome AF: 0.00136

Gnomad AMR exome AF: 0.00153

Gnomad ASJ exome AF: 0.0000994

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0271

Gnomad NFE exome AF: 0.0110

Gnomad OTH exome AF: 0.00736

GnomAD4 exome AF: 0.0104 AC: 15168 AN: 1459872 Hom.: 99 Cov.: 32 AF XY: 0.0103 AC XY: 7472 AN XY: 726332

African (AFR) AF: 0.00117 AC: 39 AN: 33476

American (AMR) AF: 0.00206 AC: 92 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.000153 AC: 4 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00554 AC: 478 AN: 86252

European-Finnish (FIN) AF: 0.0269 AC: 1391 AN: 51630

Middle Eastern (MID) AF: 0.0108 AC: 62 AN: 5740

European-Non Finnish (NFE) AF: 0.0113 AC: 12575 AN: 1111862

Other (OTH) AF: 0.00873 AC: 527 AN: 60356

GnomAD4 genome AF: 0.00831 AC: 1265 AN: 152310 Hom.: 10 Cov.: 32 AF XY: 0.00875 AC XY: 652 AN XY: 74482

African (AFR) AF: 0.00197 AC: 82 AN: 41570

American (AMR) AF: 0.00262 AC: 40 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00683 AC: 33 AN: 4832

European-Finnish (FIN) AF: 0.0271 AC: 288 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0120 AC: 813 AN: 68012

Other (OTH) AF: 0.00425 AC: 9 AN: 2116

Alfa AF: 0.00730 Hom.: 5

Bravo AF: 0.00601

Asia WGS AF: 0.00462 AC: 16 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Autosomal recessive congenital ichthyosis 5 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	6.9
DANN	Benign	0.83
PhyloP100		2.1
PromoterAI		-0.0061	Neutral
Mutation Taster		=100/0	polymorphism

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: rs118091316; hg19: chr19-15636324;