2-72129320-G-T

Position:

• chr2-72129320-G-T

Variant summary

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

The NM_019885.4(CYP26B1):​c.*2907C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 152,230 control chromosomes in the GnomAD database, including 12,923 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.35 (12914 hom., cov: 33)
  • Exomes 𝑓: 0.20 (9 hom.)
• Consequence: CYP26B1 NM_019885.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.16

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.676 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP26B1	NM_019885.4	c.*2907C>A		3_prime_UTR_variant	6/6	ENST00000001146.7	NP_063938.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP26B1	ENST00000001146.7	c.*2907C>A		3_prime_UTR_variant	6/6	1	NM_019885.4	ENSP00000001146.2
CYP26B1	ENST00000546307.5	c.*2907C>A		3_prime_UTR_variant	5/5	1		ENSP00000443304.1

Frequencies

GnomAD3 genomes AF: 0.348 AC: 52840 AN: 151728 Hom.: 12875 Cov.: 33

Gnomad AFR AF: 0.682

Gnomad AMI AF: 0.0945

Gnomad AMR AF: 0.298

Gnomad ASJ AF: 0.261

Gnomad EAS AF: 0.549

Gnomad SAS AF: 0.295

Gnomad FIN AF: 0.174

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.306

GnomAD4 exome AF: 0.204 AC: 77 AN: 378 Hom.: 9 Cov.: 0 AF XY: 0.188 AC XY: 42 AN XY: 224

Gnomad4 FIN exome AF: 0.206

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.349 AC: 52939 AN: 151852 Hom.: 12914 Cov.: 33 AF XY: 0.345 AC XY: 25639 AN XY: 74232

Gnomad4 AFR AF: 0.682

Gnomad4 AMR AF: 0.298

Gnomad4 ASJ AF: 0.261

Gnomad4 EAS AF: 0.548

Gnomad4 SAS AF: 0.293

Gnomad4 FIN AF: 0.174

Gnomad4 NFE AF: 0.182

Gnomad4 OTH AF: 0.312

Alfa AF: 0.193 Hom.: 4916

Bravo AF: 0.373

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	14
DANN	Benign	0.82

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: rs707718; hg19: chr2-72356449; COSMIC: COSV50011215; COSMIC: COSV50011215;