chr2-38076389-G-A

Variant names:

• chr2-38076389-G-A
• rs2567206
• ENST00000860003.1:c.-1001C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000860003.1(CYP1B1):​c.-1001C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 164,572 control chromosomes in the GnomAD database, including 5,428 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.23 (4946 hom., cov: 33)
  • Exomes 𝑓: 0.27 (482 hom.)
• Consequence: CYP1B1 ENST00000860003.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.85
• Publications: 18 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 2-38076389-G-A is Benign according to our data. Variant chr2-38076389-G-A is described in ClinVar as Benign. ClinVar VariationId is 1170193.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.355 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000860003.1. 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.-611C>T		upstream_gene	N/A	NP_000095.2	Q16678

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP1B1	ENST00000860003.1		c.-1001C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 2	ENSP00000530062.1
	CYP1B1	ENST00000860003.1		c.-1001C>T		5_prime_UTR	Exon 1 of 2	ENSP00000530062.1
	CYP1B1	ENST00000948951.1		c.-1-1000C>T		intron	N/A	ENSP00000619010.1

Frequencies

GnomAD3 genomes AF: 0.230 AC: 34970 AN: 152044 Hom.: 4947 Cov.: 33

Gnomad AFR AF: 0.0741

Gnomad AMI AF: 0.503

Gnomad AMR AF: 0.278

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.172

Gnomad SAS AF: 0.369

Gnomad FIN AF: 0.366

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.285

Gnomad OTH AF: 0.231

GnomAD4 exome AF: 0.267 AC: 3311 AN: 12414 Hom.: 482 Cov.: 0 AF XY: 0.268 AC XY: 1758 AN XY: 6560

African (AFR) AF: 0.0709 AC: 19 AN: 268

American (AMR) AF: 0.356 AC: 89 AN: 250

Ashkenazi Jewish (ASJ) AF: 0.235 AC: 86 AN: 366

East Asian (EAS) AF: 0.107 AC: 137 AN: 1280

South Asian (SAS) AF: 0.389 AC: 42 AN: 108

European-Finnish (FIN) AF: 0.363 AC: 504 AN: 1390

Middle Eastern (MID) AF: 0.387 AC: 24 AN: 62

European-Non Finnish (NFE) AF: 0.277 AC: 2216 AN: 8006

Other (OTH) AF: 0.284 AC: 194 AN: 684

GnomAD4 genome AF: 0.230 AC: 34962 AN: 152158 Hom.: 4946 Cov.: 33 AF XY: 0.238 AC XY: 17666 AN XY: 74380

African (AFR) AF: 0.0739 AC: 3069 AN: 41552

American (AMR) AF: 0.277 AC: 4241 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.209 AC: 725 AN: 3472

East Asian (EAS) AF: 0.172 AC: 886 AN: 5152

South Asian (SAS) AF: 0.369 AC: 1781 AN: 4824

European-Finnish (FIN) AF: 0.366 AC: 3882 AN: 10602

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.285 AC: 19350 AN: 67942

Other (OTH) AF: 0.235 AC: 496 AN: 2108

Alfa AF: 0.192 Hom.: 832

Bravo AF: 0.211

Asia WGS AF: 0.268 AC: 932 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Congenital glaucoma (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	1.9
DANN	Benign	0.91
PhyloP100		-1.8
PromoterAI		-0.0032	Neutral

Splicing

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

Other links and lift over

dbSNP: rs2567206; hg19: chr2-38303531;