ENST00000494864.1:c.-70-9409G>A

Variant names:

• chr2-38080719-C-T
• rs10175368
• ENST00000494864.1:c.-70-9409G>A

Variant summary

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

The ENST00000494864.1(CYP1B1):​c.-70-9409G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 152,036 control chromosomes in the GnomAD database, including 4,942 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 0.23 (4942 hom., cov: 32)
• Consequence: CYP1B1 ENST00000494864.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13
• Publications: 19 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=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.354 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP1B1	ENST00000494864.1	TSL:5	c.-70-9409G>A		intron	N/A	ENSP00000479876.1
	CYP1B1-AS1	ENST00000589303.6	TSL:5	n.310+4159C>T		intron	N/A
	CYP1B1-AS1	ENST00000620177.4	TSL:4	n.421+4651C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35184 AN: 151918 Hom.: 4943 Cov.: 32

Gnomad AFR AF: 0.0811

Gnomad AMI AF: 0.503

Gnomad AMR AF: 0.276

Gnomad ASJ AF: 0.211

Gnomad EAS AF: 0.171

Gnomad SAS AF: 0.368

Gnomad FIN AF: 0.368

Gnomad MID AF: 0.274

Gnomad NFE AF: 0.284

Gnomad OTH AF: 0.233

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

GnomAD4 genome AF: 0.231 AC: 35176 AN: 152036 Hom.: 4942 Cov.: 32 AF XY: 0.239 AC XY: 17764 AN XY: 74312

African (AFR) AF: 0.0809 AC: 3355 AN: 41488

American (AMR) AF: 0.275 AC: 4208 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.211 AC: 733 AN: 3472

East Asian (EAS) AF: 0.171 AC: 882 AN: 5172

South Asian (SAS) AF: 0.368 AC: 1772 AN: 4816

European-Finnish (FIN) AF: 0.368 AC: 3885 AN: 10550

Middle Eastern (MID) AF: 0.257 AC: 75 AN: 292

European-Non Finnish (NFE) AF: 0.284 AC: 19307 AN: 67950

Other (OTH) AF: 0.237 AC: 500 AN: 2108

Alfa AF: 0.262 Hom.: 7905

Bravo AF: 0.213

Asia WGS AF: 0.265 AC: 921 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.021
DANN	Benign	0.62
PhyloP100		-1.1

Splicing

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

Other links and lift over

dbSNP: rs10175368; hg19: chr2-38307861;