rs2241057

Variant names:

• chr2-72134831-A-C
• rs2241057
• NM_019885.4:c.791T>G

Your query was ambiguous. Multiple possible variants found:

• chr2-72134831-A-C
• chr2-72134831-A-G
• chr2-72134831-A-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_019885.4(CYP26B1):​c.791T>G​(p.Leu264Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. L264S) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CYP26B1 NM_019885.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.56
• Publications: 0 publications found

Genes affected

CYP26B1 (HGNC:20581): (cytochrome P450 family 26 subfamily B member 1) This gene encodes a member of the cytochrome P450 superfamily. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. The encoded protein is localized to the endoplasmic reticulum, and functions as a critical regulator of all-trans retinoic acid levels by the specific inactivation of all-trans retinoic acid to hydroxylated forms. Mutations in this gene are associated with radiohumeral fusions and other skeletal and craniofacial anomalies, and increased levels of the encoded protein are associated with atherosclerotic lesions. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2013]

CYP26B1 Gene-Disease associations (from GenCC):

• lethal occipital encephalocele-skeletal dysplasia syndrome

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23122126).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019885.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP26B1	NM_019885.4	MANE Select	c.791T>G	p.Leu264Trp	missense	Exon 4 of 6	NP_063938.1
	CYP26B1	NM_001277742.2		c.566T>G	p.Leu189Trp	missense	Exon 3 of 5	NP_001264671.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP26B1	ENST00000001146.7	TSL:1 MANE Select	c.791T>G	p.Leu264Trp	missense	Exon 4 of 6	ENSP00000001146.2
	CYP26B1	ENST00000546307.5	TSL:1	c.566T>G	p.Leu189Trp	missense	Exon 3 of 5	ENSP00000443304.1
	CYP26B1	ENST00000412253.1	TSL:1	c.218T>G	p.Leu73Trp	missense	Exon 3 of 5	ENSP00000401465.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.095	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	22
DANN	Benign	0.92
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.29	T
M_CAP	Benign	0.067	D
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.65	T
MutationAssessor	Benign	0.55	N
PhyloP100		2.6
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.48	N
REVEL	Benign	0.081
Sift	Uncertain	0.014	D
Sift4G	Uncertain	0.016	D
Polyphen		0.21	B
Vest4		0.26
MutPred		0.41		Loss of disorder (P = 0.0266)
MVP		0.33
MPC		0.55
ClinPred		0.24	T
GERP RS		3.3
Varity_R		0.18
gMVP		0.31
Mutation Taster		=95/5	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: rs2241057; hg19: chr2-72361960;