2-38089429-C-A

Variant names:

• chr2-38089429-C-A
• rs151096
• ENST00000494864.1:c.-70-18119G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000494864.1(CYP1B1):​c.-70-18119G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.451 in 152,168 control chromosomes in the GnomAD database, including 18,745 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 0.45 (18745 hom., cov: 33)
• Consequence: CYP1B1 ENST00000494864.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.527
• Publications: 8 publications found

Genes affected

CYP1B1 (HGNC:2597): (cytochrome P450 family 1 subfamily B member 1) This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. The enzyme encoded by this gene localizes to the endoplasmic reticulum and metabolizes procarcinogens such as polycyclic aromatic hydrocarbons and 17beta-estradiol. Mutations in this gene have been associated with primary congenital glaucoma; therefore it is thought that the enzyme also metabolizes a signaling molecule involved in eye development, possibly a steroid. [provided by RefSeq, Jul 2008]

CYP1B1-AS1 (HGNC:28543): (CYP1B1 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.857 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP1B1	ENST00000494864.1	c.-70-18119G>T		intron_variant	Intron 1 of 1	5		ENSP00000479876.1
CYP1B1-AS1	ENST00000589303.6	n.310+12869C>A		intron_variant	Intron 1 of 3	5
CYP1B1-AS1	ENST00000620177.4	n.421+13361C>A		intron_variant	Intron 1 of 2	4

Frequencies

GnomAD3 genomes AF: 0.451 AC: 68648 AN: 152050 Hom.: 18746 Cov.: 33

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.527

Gnomad AMR AF: 0.606

Gnomad ASJ AF: 0.452

Gnomad EAS AF: 0.879

Gnomad SAS AF: 0.793

Gnomad FIN AF: 0.582

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.523

Gnomad OTH AF: 0.502

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

GnomAD4 genome AF: 0.451 AC: 68645 AN: 152168 Hom.: 18745 Cov.: 33 AF XY: 0.465 AC XY: 34622 AN XY: 74386

African (AFR) AF: 0.145 AC: 6026 AN: 41530

American (AMR) AF: 0.606 AC: 9260 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.452 AC: 1571 AN: 3472

East Asian (EAS) AF: 0.878 AC: 4551 AN: 5182

South Asian (SAS) AF: 0.794 AC: 3829 AN: 4824

European-Finnish (FIN) AF: 0.582 AC: 6150 AN: 10574

Middle Eastern (MID) AF: 0.551 AC: 162 AN: 294

European-Non Finnish (NFE) AF: 0.523 AC: 35542 AN: 67982

Other (OTH) AF: 0.508 AC: 1074 AN: 2116

Alfa AF: 0.497 Hom.: 50323

Bravo AF: 0.438

Asia WGS AF: 0.777 AC: 2699 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.9
DANN	Benign	0.70
PhyloP100		0.53

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs151096; hg19: chr2-38316571;