2-72141061-C-G

Position:

• chr2-72141061-C-G

Variant summary

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

The NM_019885.4(CYP26B1):​c.429+2928G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 152,164 control chromosomes in the GnomAD database, including 14,890 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 0.29 (14890 hom., cov: 33)
• Consequence: CYP26B1 NM_019885.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.729

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.817 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP26B1	NM_019885.4	c.429+2928G>C		intron_variant		ENST00000001146.7	NP_063938.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP26B1	ENST00000001146.7	c.429+2928G>C		intron_variant		1	NM_019885.4	ENSP00000001146.2

Frequencies

GnomAD3 genomes AF: 0.293 AC: 44494 AN: 152046 Hom.: 14821 Cov.: 33

Gnomad AFR AF: 0.824

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.0416

Gnomad SAS AF: 0.0354

Gnomad FIN AF: 0.0718

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.0857

Gnomad OTH AF: 0.237

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.293 AC: 44625 AN: 152164 Hom.: 14890 Cov.: 33 AF XY: 0.284 AC XY: 21109 AN XY: 74388

Gnomad4 AFR AF: 0.825

Gnomad4 AMR AF: 0.162

Gnomad4 ASJ AF: 0.103

Gnomad4 EAS AF: 0.0417

Gnomad4 SAS AF: 0.0338

Gnomad4 FIN AF: 0.0718

Gnomad4 NFE AF: 0.0857

Gnomad4 OTH AF: 0.242

Alfa AF: 0.0470 Hom.: 74

Asia WGS AF: 0.116 AC: 405 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.12
DANN	Benign	0.75

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: rs3768641; hg19: chr2-72368190;