rs2617266

Variant names:

• chr2-38075401-G-A
• rs2617266
• NM_000104.4:c.-1-12C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000104.4(CYP1B1):​c.-1-12C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 1,609,792 control chromosomes in the GnomAD database, including 66,035 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★★). The gene CYP1B1 is included in the ClinGen Criteria Specification Registry.

• Frequency:
  • Genomes: 𝑓 0.28 (6311 hom., cov: 33)
  • Exomes 𝑓: 0.28 (59724 hom.)
• Consequence: CYP1B1 NM_000104.4 intron
• Scores: Splicing: ADA: 0.00001679
• Clinical Significance: Benign reviewed by expert panel B:9
• Conservation: PhyloP100: 0.0280
• Publications: 34 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

Specifications for CYP1B1 are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 2-38075401-G-A is Benign according to our data. Variant chr2-38075401-G-A is described in ClinVar as Benign. ClinVar VariationId is 166974.Status of the report is reviewed_by_expert_panel, 3 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.365 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000104.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP1B1	NM_000104.4	MANE Select	c.-1-12C>T		intron	N/A	NP_000095.2	Q16678

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP1B1	ENST00000610745.5	TSL:1 MANE Select	c.-1-12C>T		intron	N/A	ENSP00000478561.1	Q16678
	CYP1B1	ENST00000860003.1		c.-13C>T		5_prime_UTR	Exon 1 of 2	ENSP00000530062.1
	CYP1B1	ENST00000490576.2	TSL:4	c.-1-12C>T		intron	N/A	ENSP00000478839.2	Q16678

Frequencies

GnomAD3 genomes AF: 0.283 AC: 42994 AN: 152072 Hom.: 6305 Cov.: 33

Gnomad AFR AF: 0.258

Gnomad AMI AF: 0.506

Gnomad AMR AF: 0.293

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.379

Gnomad FIN AF: 0.366

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.285

Gnomad OTH AF: 0.265

GnomAD2 exomes AF: 0.293 AC: 70960 AN: 242504 AF XY: 0.297

Gnomad AFR exome AF: 0.262

Gnomad AMR exome AF: 0.295

Gnomad ASJ exome AF: 0.222

Gnomad EAS exome AF: 0.189

Gnomad FIN exome AF: 0.359

Gnomad NFE exome AF: 0.286

Gnomad OTH exome AF: 0.291

GnomAD4 exome AF: 0.283 AC: 412441 AN: 1457602 Hom.: 59724 Cov.: 34 AF XY: 0.286 AC XY: 207294 AN XY: 724966

African (AFR) AF: 0.262 AC: 8749 AN: 33412

American (AMR) AF: 0.294 AC: 13070 AN: 44500

Ashkenazi Jewish (ASJ) AF: 0.224 AC: 5839 AN: 26078

East Asian (EAS) AF: 0.148 AC: 5872 AN: 39648

South Asian (SAS) AF: 0.368 AC: 31571 AN: 85848

European-Finnish (FIN) AF: 0.358 AC: 18550 AN: 51804

Middle Eastern (MID) AF: 0.307 AC: 1442 AN: 4690

European-Non Finnish (NFE) AF: 0.279 AC: 310442 AN: 1111448

Other (OTH) AF: 0.281 AC: 16906 AN: 60174

GnomAD4 genome AF: 0.283 AC: 43021 AN: 152190 Hom.: 6311 Cov.: 33 AF XY: 0.288 AC XY: 21429 AN XY: 74388

African (AFR) AF: 0.258 AC: 10726 AN: 41528

American (AMR) AF: 0.292 AC: 4475 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.209 AC: 724 AN: 3470

East Asian (EAS) AF: 0.180 AC: 930 AN: 5156

South Asian (SAS) AF: 0.379 AC: 1830 AN: 4826

European-Finnish (FIN) AF: 0.366 AC: 3877 AN: 10590

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.285 AC: 19347 AN: 67998

Other (OTH) AF: 0.272 AC: 575 AN: 2116

Alfa AF: 0.284 Hom.: 1257

Bravo AF: 0.271

Asia WGS AF: 0.296 AC: 1028 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: reviewed by expert panel

Pathogenic	VUS	Benign	Condition
-	-	2	Glaucoma 3A (2)
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	1	Anterior segment dysgenesis 6 (1)
-	-	1	CYP1B1-related glaucoma with or without anterior segment dysgenesis (1)
-	-	1	Irido-corneo-trabecular dysgenesis (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	10
DANN	Benign	0.93
PhyloP100		0.028
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000017
dbscSNV1_RF	Benign	0.040
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs2617266; hg19: chr2-38302544; COSMIC: COSV53191821; COSMIC: COSV53191821;