2-38080367-T-C

Variant names:

• chr2-38080367-T-C
• rs162555
• ENST00000494864.1:c.-70-9057A>G

Variant summary

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

The ENST00000494864.1(CYP1B1):​c.-70-9057A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 152,070 control chromosomes in the GnomAD database, including 2,490 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 0.18 (2490 hom., cov: 32)
• Consequence: CYP1B1 ENST00000494864.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.942
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP1B1	ENST00000494864.1	c.-70-9057A>G		intron_variant	Intron 1 of 1	5		ENSP00000479876.1
CYP1B1-AS1	ENST00000589303.6	n.310+3807T>C		intron_variant	Intron 1 of 3	5
CYP1B1-AS1	ENST00000620177.4	n.421+4299T>C		intron_variant	Intron 1 of 2	4

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26739 AN: 151952 Hom.: 2490 Cov.: 32

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.0614

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.194

Gnomad EAS AF: 0.0201

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.193

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

GnomAD4 genome AF: 0.176 AC: 26758 AN: 152070 Hom.: 2490 Cov.: 32 AF XY: 0.169 AC XY: 12554 AN XY: 74330

African (AFR) AF: 0.183 AC: 7587 AN: 41478

American (AMR) AF: 0.159 AC: 2422 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.194 AC: 672 AN: 3468

East Asian (EAS) AF: 0.0201 AC: 104 AN: 5170

South Asian (SAS) AF: 0.105 AC: 508 AN: 4816

European-Finnish (FIN) AF: 0.115 AC: 1217 AN: 10590

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.202 AC: 13735 AN: 67964

Other (OTH) AF: 0.190 AC: 400 AN: 2104

Alfa AF: 0.192 Hom.: 4003

Bravo AF: 0.182

Asia WGS AF: 0.0790 AC: 278 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.9
DANN	Benign	0.78
PhyloP100		-0.94

Splicing

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

Other links and lift over

dbSNP: rs162555; hg19: chr2-38307509;