2-72132271-C-G

Variant names:

• chr2-72132271-C-G
• NM_019885.4:c.1495G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_019885.4(CYP26B1):​c.1495G>C​(p.Glu499Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000207 in 1,452,640 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: CYP26B1 NM_019885.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.30

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07151133).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP26B1	NM_019885.4	c.1495G>C	p.Glu499Gln	missense_variant	Exon 6 of 6	ENST00000001146.7	NP_063938.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP26B1	ENST00000001146.7	c.1495G>C	p.Glu499Gln	missense_variant	Exon 6 of 6	1	NM_019885.4	ENSP00000001146.2
CYP26B1	ENST00000546307.5	c.1270G>C	p.Glu424Gln	missense_variant	Exon 5 of 5	1		ENSP00000443304.1
CYP26B1	ENST00000412253.1	c.922G>C	p.Glu308Gln	missense_variant	Exon 5 of 5	1		ENSP00000401465.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000207 AC: 3 AN: 1452640 Hom.: 0 Cov.: 32 AF XY: 0.00000277 AC XY: 2 AN XY: 721640

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000118

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.02e-7

Gnomad4 OTH exome AF: 0.0000167

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.12	.;T;.
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.43
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.46	T;T;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.072	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	.;L;.
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.36	N;N;N
REVEL	Benign	0.068
Sift	Benign	0.16	T;T;T
Sift4G	Benign	0.34	T;T;T
Polyphen		0.0	.;B;.
Vest4		0.077
MutPred		0.38		.;Loss of sheet (P = 0.0457);.;
MVP		0.58
MPC		0.28
ClinPred		0.16	T
GERP RS		2.1
Varity_R		0.073
gMVP		0.67

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-72359400;