2-72141061-C-G

Variant names:

• chr2-72141061-C-G
• rs3768641
• NM_019885.4:c.429+2928G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 20 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: Benign. The variant received -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 rank	MANE	Protein	UniProt
CYP26B1	NM_019885.4	c.429+2928G>C		intron_variant	Intron 2 of 5	ENST00000001146.7	NP_063938.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP26B1	ENST00000001146.7	c.429+2928G>C		intron_variant	Intron 2 of 5	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

African (AFR) AF: 0.825 AC: 34230 AN: 41502

American (AMR) AF: 0.162 AC: 2480 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 356 AN: 3470

East Asian (EAS) AF: 0.0417 AC: 215 AN: 5156

South Asian (SAS) AF: 0.0338 AC: 163 AN: 4826

European-Finnish (FIN) AF: 0.0718 AC: 762 AN: 10606

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.0857 AC: 5827 AN: 67992

Other (OTH) AF: 0.242 AC: 511 AN: 2112

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
PhyloP100		-0.73
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: rs3768641; hg19: chr2-72368190;