2-38080501-G-T

Variant names:

• chr2-38080501-G-T
• rs10175338
• ENST00000494864.1:c.-70-9191C>A

Variant summary

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

The ENST00000494864.1(CYP1B1):​c.-70-9191C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 152,054 control chromosomes in the GnomAD database, including 5,411 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 0.26 (5411 hom., cov: 32)
• Consequence: CYP1B1 ENST00000494864.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21
• Publications: 14 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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.362 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP1B1	ENST00000494864.1	TSL:5	c.-70-9191C>A		intron	N/A	ENSP00000479876.1
	CYP1B1-AS1	ENST00000589303.6	TSL:5	n.310+3941G>T		intron	N/A
	CYP1B1-AS1	ENST00000620177.4	TSL:4	n.421+4433G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.256 AC: 38900 AN: 151936 Hom.: 5413 Cov.: 32

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.503

Gnomad AMR AF: 0.285

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.172

Gnomad SAS AF: 0.376

Gnomad FIN AF: 0.365

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.284

Gnomad OTH AF: 0.248

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

GnomAD4 genome AF: 0.256 AC: 38894 AN: 152054 Hom.: 5411 Cov.: 32 AF XY: 0.263 AC XY: 19560 AN XY: 74336

African (AFR) AF: 0.165 AC: 6851 AN: 41464

American (AMR) AF: 0.284 AC: 4343 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.212 AC: 736 AN: 3466

East Asian (EAS) AF: 0.172 AC: 887 AN: 5162

South Asian (SAS) AF: 0.376 AC: 1812 AN: 4816

European-Finnish (FIN) AF: 0.365 AC: 3866 AN: 10578

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.284 AC: 19331 AN: 67964

Other (OTH) AF: 0.252 AC: 533 AN: 2114

Alfa AF: 0.274 Hom.: 9646

Bravo AF: 0.240

Asia WGS AF: 0.278 AC: 968 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.040
DANN	Benign	0.44
PhyloP100		-1.2

Splicing

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

Other links and lift over

dbSNP: rs10175338; hg19: chr2-38307643;