rs201284617

chr10-93062161-A-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_183374.3(CYP26C1):c.356A>C(p.Gln119Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00103 in 1,540,496 control chromosomes in the GnomAD database, including 13 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 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00089 (12 hom.)
• Consequence: CYP26C1 NM_183374.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.81

Genes affected

CYP26C1 (HGNC:20577): (cytochrome P450 family 26 subfamily C member 1) 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 enzyme is involved in the catabolism of all-trans- and 9-cis-retinoic acid, and thus contributes to the regulation of retinoic acid levels in cells and tissues. This gene is adjacent to a related gene on chromosome 10q23.33. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.012394369).
• BS2: High Homozygotes in GnomAdExome at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP26C1	NM_183374.3	c.356A>C	p.Gln119Pro	missense_variant	2/6	ENST00000651965.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP26C1	ENST00000651965.1	c.356A>C	p.Gln119Pro	missense_variant	2/6		NM_183374.3	P1
CYP26C1	ENST00000624358.3	c.356A>C	p.Gln119Pro	missense_variant, NMD_transcript_variant	2/6	2

Frequencies

GnomAD3 genomes AF: 0.00227 AC: 345 AN: 152238 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00424

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0263

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000632

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00162 AC: 223 AN: 137874 Hom.: 3 AF XY: 0.00143 AC XY: 106 AN XY: 74188

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00233

Gnomad SAS exome AF: 0.000177

Gnomad FIN exome AF: 0.0227

Gnomad NFE exome AF: 0.000269

Gnomad OTH exome AF: 0.000719

GnomAD4 exome AF: 0.000893 AC: 1240 AN: 1388140 Hom.: 12 Cov.: 32 AF XY: 0.000850 AC XY: 582 AN XY: 685100

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00459

Gnomad4 SAS exome AF: 0.000126

Gnomad4 FIN exome AF: 0.0204

Gnomad4 NFE exome AF: 0.000203

Gnomad4 OTH exome AF: 0.00100

GnomAD4 genome AF: 0.00226 AC: 345 AN: 152356 Hom.: 1 Cov.: 33 AF XY: 0.00319 AC XY: 238 AN XY: 74500

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00425

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.0263

Gnomad4 NFE AF: 0.000632

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000530 Hom.: 0

Bravo AF: 0.000295

ExAC AF: 0.000799 AC: 64

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Optic nerve hypoplasia Benign:1

Likely benign, criteria provided, single submitter

research

Rare Disease Group, Clinical Genetics, Karolinska Institutet

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.13
Cadd	Uncertain	25
Dann	Uncertain	0.99
DEOGEN2	Benign	0.32	T
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.045	D
MetaRNN	Benign	0.012	T
MetaSVM	Benign	-0.72	T
MutationAssessor	Benign	1.5	L
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-3.3	D
REVEL	Uncertain	0.40
Sift	Benign	0.18	T
Sift4G	Benign	0.11	T
Polyphen		0.96	D
Vest4		0.60
MVP		0.91
MPC		1.5
ClinPred		0.082	T
GERP RS		5.7
Varity_R		0.74

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: rs201284617; hg19: chr10-94821918;