ENST00000494864.1:c.-71+19101C>T

Variant names:

• chr2-38090568-G-A
• rs4670813
• ENST00000494864.1:c.-71+19101C>T

Variant summary

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

The ENST00000494864.1(CYP1B1):​c.-71+19101C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.409 in 152,102 control chromosomes in the GnomAD database, including 15,766 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. The gene CYP1B1 is included in the ClinGen Criteria Specification Registry.

• Frequency: Genomes: 𝑓 0.41 (15766 hom., cov: 33)
• Consequence: CYP1B1 ENST00000494864.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.02
• Publications: 11 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

Specifications for CYP1B1 are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.773 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000494864.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP1B1	ENST00000494864.1	TSL:5	c.-71+19101C>T		intron	N/A	ENSP00000479876.1	A0A087WW26
	CYP1B1-AS1	ENST00000589303.6	TSL:5	n.310+14008G>A		intron	N/A
	CYP1B1-AS1	ENST00000620177.4	TSL:4	n.421+14500G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.410 AC: 62240 AN: 151982 Hom.: 15771 Cov.: 33

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.478

Gnomad AMR AF: 0.566

Gnomad ASJ AF: 0.391

Gnomad EAS AF: 0.794

Gnomad SAS AF: 0.693

Gnomad FIN AF: 0.538

Gnomad MID AF: 0.471

Gnomad NFE AF: 0.486

Gnomad OTH AF: 0.446

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

GnomAD4 genome AF: 0.409 AC: 62237 AN: 152102 Hom.: 15766 Cov.: 33 AF XY: 0.421 AC XY: 31322 AN XY: 74356

African (AFR) AF: 0.110 AC: 4559 AN: 41482

American (AMR) AF: 0.565 AC: 8652 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.391 AC: 1358 AN: 3472

East Asian (EAS) AF: 0.793 AC: 4111 AN: 5182

South Asian (SAS) AF: 0.693 AC: 3341 AN: 4822

European-Finnish (FIN) AF: 0.538 AC: 5685 AN: 10564

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.486 AC: 33012 AN: 67966

Other (OTH) AF: 0.448 AC: 946 AN: 2110

Alfa AF: 0.327 Hom.: 1716

Bravo AF: 0.397

Asia WGS AF: 0.688 AC: 2390 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.5
DANN	Benign	0.77
PhyloP100		1.0

Splicing

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

Other links and lift over

dbSNP: rs4670813; hg19: chr2-38317710;