rs162556

Variant names:

• chr2-38079312-G-A
• rs162556
• ENST00000494864.1:c.-70-8002C>T

Variant summary

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

The ENST00000494864.1(CYP1B1):​c.-70-8002C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.616 in 152,198 control chromosomes in the GnomAD database, including 31,452 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 0.62 (31452 hom., cov: 33)
• Consequence: CYP1B1 ENST00000494864.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.120
• Publications: 21 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.888 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.-70-8002C>T		intron_variant	Intron 1 of 1	5		ENSP00000479876.1
CYP1B1-AS1	ENST00000589303.6	n.310+2752G>A		intron_variant	Intron 1 of 3	5
CYP1B1-AS1	ENST00000620177.4	n.421+3244G>A		intron_variant	Intron 1 of 2	4

Frequencies

GnomAD3 genomes AF: 0.616 AC: 93627 AN: 152080 Hom.: 31395 Cov.: 33

Gnomad AFR AF: 0.895

Gnomad AMI AF: 0.648

Gnomad AMR AF: 0.533

Gnomad ASJ AF: 0.537

Gnomad EAS AF: 0.202

Gnomad SAS AF: 0.500

Gnomad FIN AF: 0.511

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.525

Gnomad OTH AF: 0.583

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

GnomAD4 genome AF: 0.616 AC: 93743 AN: 152198 Hom.: 31452 Cov.: 33 AF XY: 0.610 AC XY: 45427 AN XY: 74414

African (AFR) AF: 0.896 AC: 37218 AN: 41560

American (AMR) AF: 0.532 AC: 8140 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.537 AC: 1865 AN: 3472

East Asian (EAS) AF: 0.202 AC: 1045 AN: 5178

South Asian (SAS) AF: 0.500 AC: 2410 AN: 4820

European-Finnish (FIN) AF: 0.511 AC: 5399 AN: 10570

Middle Eastern (MID) AF: 0.595 AC: 175 AN: 294

European-Non Finnish (NFE) AF: 0.525 AC: 35664 AN: 67992

Other (OTH) AF: 0.586 AC: 1239 AN: 2114

Alfa AF: 0.557 Hom.: 40895

Bravo AF: 0.627

Asia WGS AF: 0.408 AC: 1423 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.80
DANN	Benign	0.56
PhyloP100		-0.12

Splicing

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

Other links and lift over

dbSNP: rs162556; hg19: chr2-38306454;