2-38101728-G-A

Variant names:

• chr2-38101728-G-A
• rs56058466
• ENST00000494864.1:c.-71+7941C>T

Variant summary

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

The ENST00000494864.1(CYP1B1):​c.-71+7941C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 151,936 control chromosomes in the GnomAD database, including 2,282 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 0.14 (2282 hom., cov: 32)
• Consequence: CYP1B1 ENST00000494864.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.180
• Publications: 2 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.294 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000494864.1. 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

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP1B1	ENST00000494864.1	TSL:5	c.-71+7941C>T		intron	N/A	ENSP00000479876.1
	CYP1B1-AS1	ENST00000427168.6	TSL:4	n.177+2972G>A		intron	N/A
	CYP1B1-AS1	ENST00000589303.6	TSL:5	n.311-20257G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21620 AN: 151818 Hom.: 2272 Cov.: 32

Gnomad AFR AF: 0.298

Gnomad AMI AF: 0.238

Gnomad AMR AF: 0.0773

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.0133

Gnomad SAS AF: 0.0724

Gnomad FIN AF: 0.0693

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.0868

Gnomad OTH AF: 0.121

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

GnomAD4 genome AF: 0.143 AC: 21678 AN: 151936 Hom.: 2282 Cov.: 32 AF XY: 0.138 AC XY: 10274 AN XY: 74256

African (AFR) AF: 0.298 AC: 12335 AN: 41396

American (AMR) AF: 0.0772 AC: 1179 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.169 AC: 585 AN: 3470

East Asian (EAS) AF: 0.0134 AC: 69 AN: 5162

South Asian (SAS) AF: 0.0729 AC: 351 AN: 4818

European-Finnish (FIN) AF: 0.0693 AC: 730 AN: 10532

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.0868 AC: 5899 AN: 67958

Other (OTH) AF: 0.121 AC: 257 AN: 2116

Alfa AF: 0.0917 Hom.: 344

Bravo AF: 0.150

Asia WGS AF: 0.0690 AC: 239 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.8
DANN	Benign	0.44
PhyloP100		-0.18

Splicing

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

Other links and lift over

dbSNP: rs56058466; hg19: chr2-38328870;