ENST00000494864.1:c.-71+4508G>A

Variant names:

• chr2-38105161-C-T
• rs232535
• ENST00000494864.1:c.-71+4508G>A

Variant summary

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

The ENST00000494864.1(CYP1B1):​c.-71+4508G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 152,030 control chromosomes in the GnomAD database, including 10,997 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 0.36 (10997 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CYP1B1 ENST00000494864.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.141
• Publications: 5 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 (AFR) allele frequency at 95% confidence interval = 0.522 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.-71+4508G>A		intron_variant	Intron 1 of 1	5		ENSP00000479876.1
CYP1B1-AS1	ENST00000427168.6	n.177+6405C>T		intron_variant	Intron 1 of 2	4
CYP1B1-AS1	ENST00000589303.6	n.311-16824C>T		intron_variant	Intron 1 of 3	5

Frequencies

GnomAD3 genomes AF: 0.364 AC: 55281 AN: 151912 Hom.: 10979 Cov.: 32

Gnomad AFR AF: 0.527

Gnomad AMI AF: 0.252

Gnomad AMR AF: 0.312

Gnomad ASJ AF: 0.297

Gnomad EAS AF: 0.0852

Gnomad SAS AF: 0.331

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.317

Gnomad OTH AF: 0.370

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.364 AC: 55340 AN: 152030 Hom.: 10997 Cov.: 32 AF XY: 0.361 AC XY: 26824 AN XY: 74312

African (AFR) AF: 0.527 AC: 21866 AN: 41454

American (AMR) AF: 0.311 AC: 4755 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.297 AC: 1030 AN: 3464

East Asian (EAS) AF: 0.0848 AC: 440 AN: 5190

South Asian (SAS) AF: 0.331 AC: 1591 AN: 4810

European-Finnish (FIN) AF: 0.286 AC: 3019 AN: 10552

Middle Eastern (MID) AF: 0.395 AC: 116 AN: 294

European-Non Finnish (NFE) AF: 0.317 AC: 21513 AN: 67964

Other (OTH) AF: 0.370 AC: 780 AN: 2108

Alfa AF: 0.357 Hom.: 2003

Bravo AF: 0.372

Asia WGS AF: 0.240 AC: 836 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	12
DANN	Benign	0.92
PhyloP100		0.14

Splicing

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

Other links and lift over

dbSNP: rs232535; hg19: chr2-38332303;