rs11666601

Variant names:

• chr19-15537904-G-A
• rs11666601
• NM_173483.4:c.582G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-15537904-G-A
• chr19-15537904-G-C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_173483.4(CYP4F22):​c.582G>A​(p.Ala194Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 1,613,962 control chromosomes in the GnomAD database, including 10,055 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.093 (744 hom., cov: 31)
  • Exomes 𝑓: 0.11 (9311 hom.)
• Consequence: CYP4F22 NM_173483.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.167
• Publications: 15 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, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• lamellar ichthyosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 19-15537904-G-A is Benign according to our data. Variant chr19-15537904-G-A is described in ClinVar as Benign. ClinVar VariationId is 262835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.167 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.114 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.582G>A	p.Ala194Ala	synonymous	Exon 7 of 14	NP_775754.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP4F22	ENST00000269703.8	TSL:2 MANE Select	c.582G>A	p.Ala194Ala	synonymous	Exon 7 of 14	ENSP00000269703.1
	CYP4F22	ENST00000601005.2	TSL:5	c.582G>A	p.Ala194Ala	synonymous	Exon 5 of 12	ENSP00000469866.1
	CYP4F22	ENST00000894419.1		c.582G>A	p.Ala194Ala	synonymous	Exon 8 of 15	ENSP00000564478.1

Frequencies

GnomAD3 genomes AF: 0.0930 AC: 14137 AN: 152054 Hom.: 742 Cov.: 31

Gnomad AFR AF: 0.0563

Gnomad AMI AF: 0.0987

Gnomad AMR AF: 0.0798

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.0693

Gnomad SAS AF: 0.0923

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.116

Gnomad OTH AF: 0.102

GnomAD2 exomes AF: 0.0960 AC: 24148 AN: 251458 AF XY: 0.0991

Gnomad AFR exome AF: 0.0536

Gnomad AMR exome AF: 0.0558

Gnomad ASJ exome AF: 0.133

Gnomad EAS exome AF: 0.0787

Gnomad FIN exome AF: 0.104

Gnomad NFE exome AF: 0.112

Gnomad OTH exome AF: 0.102

GnomAD4 exome AF: 0.111 AC: 161862 AN: 1461790 Hom.: 9311 Cov.: 35 AF XY: 0.110 AC XY: 80312 AN XY: 727190

African (AFR) AF: 0.0557 AC: 1866 AN: 33478

American (AMR) AF: 0.0585 AC: 2617 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.135 AC: 3533 AN: 26136

East Asian (EAS) AF: 0.0513 AC: 2037 AN: 39700

South Asian (SAS) AF: 0.0942 AC: 8122 AN: 86256

European-Finnish (FIN) AF: 0.103 AC: 5491 AN: 53402

Middle Eastern (MID) AF: 0.132 AC: 752 AN: 5714

European-Non Finnish (NFE) AF: 0.118 AC: 130688 AN: 1111992

Other (OTH) AF: 0.112 AC: 6756 AN: 60388

GnomAD4 genome AF: 0.0930 AC: 14156 AN: 152172 Hom.: 744 Cov.: 31 AF XY: 0.0921 AC XY: 6851 AN XY: 74380

African (AFR) AF: 0.0564 AC: 2343 AN: 41526

American (AMR) AF: 0.0797 AC: 1218 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 454 AN: 3466

East Asian (EAS) AF: 0.0695 AC: 360 AN: 5182

South Asian (SAS) AF: 0.0934 AC: 450 AN: 4818

European-Finnish (FIN) AF: 0.102 AC: 1082 AN: 10588

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.116 AC: 7907 AN: 67998

Other (OTH) AF: 0.100 AC: 212 AN: 2112

Alfa AF: 0.108 Hom.: 2118

Bravo AF: 0.0889

Asia WGS AF: 0.0770 AC: 269 AN: 3478

EpiCase AF: 0.118

EpiControl AF: 0.119

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	9.7
DANN	Benign	0.49
PhyloP100		0.17
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: rs11666601; hg19: chr19-15648715; COSMIC: COSV54112318;