2-38078309-A-G

Variant names:

• chr2-38078309-A-G
• rs162557
• ENST00000948951.1:c.-1-2920T>C

Variant summary

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

The ENST00000948951.1(CYP1B1):​c.-1-2920T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.781 in 152,030 control chromosomes in the GnomAD database, including 46,562 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 0.78 (46562 hom., cov: 31)
• Consequence: CYP1B1 ENST00000948951.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.615
• Publications: 13 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=-0.78).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.892 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

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	ENST00000948951.1		c.-1-2920T>C		intron	N/A	ENSP00000619010.1
	CYP1B1	ENST00000494864.1	TSL:5	c.-70-6999T>C		intron	N/A	ENSP00000479876.1
	CYP1B1-AS1	ENST00000589303.6	TSL:5	n.310+1749A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.781 AC: 118611 AN: 151912 Hom.: 46535 Cov.: 31

Gnomad AFR AF: 0.771

Gnomad AMI AF: 0.704

Gnomad AMR AF: 0.858

Gnomad ASJ AF: 0.703

Gnomad EAS AF: 0.904

Gnomad SAS AF: 0.915

Gnomad FIN AF: 0.752

Gnomad MID AF: 0.861

Gnomad NFE AF: 0.758

Gnomad OTH AF: 0.808

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

GnomAD4 genome AF: 0.781 AC: 118697 AN: 152030 Hom.: 46562 Cov.: 31 AF XY: 0.785 AC XY: 58351 AN XY: 74302

African (AFR) AF: 0.771 AC: 31969 AN: 41444

American (AMR) AF: 0.858 AC: 13116 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.703 AC: 2441 AN: 3472

East Asian (EAS) AF: 0.904 AC: 4683 AN: 5182

South Asian (SAS) AF: 0.915 AC: 4408 AN: 4820

European-Finnish (FIN) AF: 0.752 AC: 7935 AN: 10546

Middle Eastern (MID) AF: 0.850 AC: 250 AN: 294

European-Non Finnish (NFE) AF: 0.758 AC: 51546 AN: 67964

Other (OTH) AF: 0.810 AC: 1708 AN: 2108

Alfa AF: 0.778 Hom.: 38107

Bravo AF: 0.789

Asia WGS AF: 0.900 AC: 3131 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	10
DANN	Benign	0.83
PhyloP100		-0.61

Splicing

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

Other links and lift over

dbSNP: rs162557; hg19: chr2-38305451;