rs11187265

Positions:

• chr10-93064409-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_183374.3(CYP26C1):​c.734G>A​(p.Arg245Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0927 in 1,613,912 control chromosomes in the GnomAD database, including 7,630 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.088 (634 hom., cov: 33)
  • Exomes 𝑓: 0.093 (6996 hom.)
• Consequence: CYP26C1 NM_183374.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.221

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]

ENSG00000285846 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0012832582).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.145 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP26C1	NM_183374.3	c.734G>A	p.Arg245Gln	missense_variant	4/6	ENST00000651965.1	NP_899230.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP26C1	ENST00000651965.1	c.734G>A	p.Arg245Gln	missense_variant	4/6		NM_183374.3	ENSP00000498424.1
ENSG00000285846	ENST00000648258.1	n.764G>A		non_coding_transcript_exon_variant	1/4
CYP26C1	ENST00000624358.3	n.*1116+94G>A		intron_variant		2		ENSP00000485098.1

Frequencies

GnomAD3 genomes AF: 0.0877 AC: 13343 AN: 152112 Hom.: 631 Cov.: 33

Gnomad AFR AF: 0.0682

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.0894

Gnomad EAS AF: 0.00347

Gnomad SAS AF: 0.0750

Gnomad FIN AF: 0.0842

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0927

Gnomad OTH AF: 0.0864

GnomAD3 exomes AF: 0.102 AC: 25664 AN: 251050 Hom.: 1827 AF XY: 0.0979 AC XY: 13288 AN XY: 135708

Gnomad AFR exome AF: 0.0661

Gnomad AMR exome AF: 0.229

Gnomad ASJ exome AF: 0.0927

Gnomad EAS exome AF: 0.00234

Gnomad SAS exome AF: 0.0859

Gnomad FIN exome AF: 0.0891

Gnomad NFE exome AF: 0.0927

Gnomad OTH exome AF: 0.102

GnomAD4 exome AF: 0.0932 AC: 136178 AN: 1461684 Hom.: 6996 Cov.: 30 AF XY: 0.0926 AC XY: 67300 AN XY: 727148

Gnomad4 AFR exome AF: 0.0662

Gnomad4 AMR exome AF: 0.218

Gnomad4 ASJ exome AF: 0.0878

Gnomad4 EAS exome AF: 0.00181

Gnomad4 SAS exome AF: 0.0883

Gnomad4 FIN exome AF: 0.0908

Gnomad4 NFE exome AF: 0.0933

Gnomad4 OTH exome AF: 0.0863

GnomAD4 genome AF: 0.0878 AC: 13368 AN: 152228 Hom.: 634 Cov.: 33 AF XY: 0.0882 AC XY: 6564 AN XY: 74426

Gnomad4 AFR AF: 0.0682

Gnomad4 AMR AF: 0.150

Gnomad4 ASJ AF: 0.0894

Gnomad4 EAS AF: 0.00347

Gnomad4 SAS AF: 0.0753

Gnomad4 FIN AF: 0.0842

Gnomad4 NFE AF: 0.0927

Gnomad4 OTH AF: 0.0897

Alfa AF: 0.0893 Hom.: 973

Bravo AF: 0.0929

TwinsUK AF: 0.0936 AC: 347

ALSPAC AF: 0.0861 AC: 332

ESP6500AA AF: 0.0704 AC: 310

ESP6500EA AF: 0.0926 AC: 796

ExAC AF: 0.0974 AC: 11820

Asia WGS AF: 0.0630 AC: 220 AN: 3478

EpiCase AF: 0.0874

EpiControl AF: 0.0900

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	2.2
DANN	Benign	0.92
DEOGEN2	Benign	0.033	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.16	T
MetaRNN	Benign	0.0013	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.18	N
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.030	N
REVEL	Benign	0.14
Sift	Benign	0.52	T
Sift4G	Benign	0.49	T
Polyphen		0.0010	B
Vest4		0.034
MPC		0.92
ClinPred		0.0065	T
GERP RS		-5.5
Varity_R		0.024

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: rs11187265; hg19: chr10-94824166; COSMIC: COSV53326560; COSMIC: COSV53326560;