2-38079273-C-G

Variant names:

• chr2-38079273-C-G
• rs4646430
• ENST00000948951.1:c.-1-3884G>C

Variant summary

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

The ENST00000948951.1(CYP1B1):​c.-1-3884G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 152,142 control chromosomes in the GnomAD database, including 4,975 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 0.23 (4975 hom., cov: 33)
• Consequence: CYP1B1 ENST00000948951.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.630
• Publications: 18 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=-0.78).
• 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: ENST00000948951.1. 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	ENST00000948951.1		c.-1-3884G>C		intron	N/A	ENSP00000619010.1
	CYP1B1	ENST00000494864.1	TSL:5	c.-70-7963G>C		intron	N/A	ENSP00000479876.1	A0A087WW26
	CYP1B1-AS1	ENST00000589303.6	TSL:5	n.310+2713C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.233 AC: 35415 AN: 152024 Hom.: 4976 Cov.: 33

Gnomad AFR AF: 0.0843

Gnomad AMI AF: 0.503

Gnomad AMR AF: 0.276

Gnomad ASJ AF: 0.211

Gnomad EAS AF: 0.171

Gnomad SAS AF: 0.376

Gnomad FIN AF: 0.368

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.285

Gnomad OTH AF: 0.234

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

GnomAD4 genome AF: 0.233 AC: 35406 AN: 152142 Hom.: 4975 Cov.: 33 AF XY: 0.240 AC XY: 17878 AN XY: 74368

African (AFR) AF: 0.0840 AC: 3487 AN: 41520

American (AMR) AF: 0.275 AC: 4209 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.211 AC: 732 AN: 3466

East Asian (EAS) AF: 0.171 AC: 884 AN: 5176

South Asian (SAS) AF: 0.377 AC: 1812 AN: 4810

European-Finnish (FIN) AF: 0.368 AC: 3884 AN: 10558

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.285 AC: 19360 AN: 68016

Other (OTH) AF: 0.239 AC: 504 AN: 2108

Alfa AF: 0.193 Hom.: 551

Bravo AF: 0.214

Asia WGS AF: 0.273 AC: 950 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	9.0
DANN	Benign	0.60
PhyloP100		0.63

Splicing

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

Other links and lift over

dbSNP: rs4646430; hg19: chr2-38306415;