rs11187265

Variant names:

• chr10-93064409-G-A
• rs11187265
• NM_183374.3:c.734G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-93064409-G-A
• chr10-93064409-G-C

Variant summary

Our verdict is Benign. The variant received -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. 16/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 19 publications found

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]

CYP26C1 Gene-Disease associations (from GenCC):

• focal facial dermal dysplasia type IV

  Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet

ENSG00000285846 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CYP26C1	NM_183374.3	c.734G>A	p.Arg245Gln	missense_variant	Exon 4 of 6	ENST00000651965.1	NP_899230.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP26C1	ENST00000651965.1	c.734G>A	p.Arg245Gln	missense_variant	Exon 4 of 6		NM_183374.3	ENSP00000498424.1
ENSG00000285846	ENST00000648258.1	n.764G>A		non_coding_transcript_exon_variant	Exon 1 of 4
CYP26C1	ENST00000624358.3	n.*1116+94G>A		intron_variant	Intron 3 of 5	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

GnomAD2 exomes AF: 0.102 AC: 25664 AN: 251050 AF XY: 0.0979

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 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

African (AFR) AF: 0.0662 AC: 2217 AN: 33480

American (AMR) AF: 0.218 AC: 9757 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.0878 AC: 2293 AN: 26128

East Asian (EAS) AF: 0.00181 AC: 72 AN: 39698

South Asian (SAS) AF: 0.0883 AC: 7620 AN: 86252

European-Finnish (FIN) AF: 0.0908 AC: 4842 AN: 53338

Middle Eastern (MID) AF: 0.0652 AC: 376 AN: 5766

European-Non Finnish (NFE) AF: 0.0933 AC: 103790 AN: 1111944

Other (OTH) AF: 0.0863 AC: 5211 AN: 60388

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

African (AFR) AF: 0.0682 AC: 2832 AN: 41542

American (AMR) AF: 0.150 AC: 2294 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0894 AC: 310 AN: 3468

East Asian (EAS) AF: 0.00347 AC: 18 AN: 5182

South Asian (SAS) AF: 0.0753 AC: 363 AN: 4820

European-Finnish (FIN) AF: 0.0842 AC: 892 AN: 10600

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.0927 AC: 6306 AN: 67996

Other (OTH) AF: 0.0897 AC: 189 AN: 2106

Alfa AF: 0.0888 Hom.: 1394

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
PhyloP100		0.22
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
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: rs11187265; hg19: chr10-94824166; COSMIC: COSV53326560; COSMIC: COSV53326560;