2-38072372-C-T

Variant names:

• chr2-38072372-C-T
• rs162560
• NM_000104.4:c.1044-1062G>A

Variant summary

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

The NM_000104.4(CYP1B1):​c.1044-1062G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 151,866 control chromosomes in the GnomAD database, including 2,695 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 0.18 (2695 hom., cov: 33)
• Consequence: CYP1B1 NM_000104.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0430
• Publications: 6 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 Gene-Disease associations (from GenCC):

• CYP1B1-related glaucoma with or without anterior segment dysgenesis

  Inheritance: AR Classification: DEFINITIVE Submitted by: Ambry Genetics, ClinGen
• glaucoma 3A

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine
• congenital glaucoma

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Peters anomaly

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.204 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.1044-1062G>A		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.1044-1062G>A		intron	N/A	ENSP00000478561.1	Q16678
	CYP1B1	ENST00000490576.2	TSL:4	c.1044-1062G>A		intron	N/A	ENSP00000478839.2	Q16678
	CYP1B1	ENST00000614273.1	TSL:5	c.1044-1062G>A		intron	N/A	ENSP00000483678.1	Q16678

Frequencies

GnomAD3 genomes AF: 0.184 AC: 27935 AN: 151748 Hom.: 2695 Cov.: 33

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.0614

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.0197

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.199

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

GnomAD4 genome AF: 0.184 AC: 27957 AN: 151866 Hom.: 2695 Cov.: 33 AF XY: 0.177 AC XY: 13124 AN XY: 74210

African (AFR) AF: 0.198 AC: 8188 AN: 41354

American (AMR) AF: 0.163 AC: 2494 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.227 AC: 787 AN: 3472

East Asian (EAS) AF: 0.0197 AC: 102 AN: 5176

South Asian (SAS) AF: 0.107 AC: 514 AN: 4812

European-Finnish (FIN) AF: 0.124 AC: 1303 AN: 10528

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.207 AC: 14035 AN: 67948

Other (OTH) AF: 0.196 AC: 413 AN: 2106

Alfa AF: 0.186 Hom.: 367

Bravo AF: 0.190

Asia WGS AF: 0.0800 AC: 279 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.5
DANN	Benign	0.54
PhyloP100		0.043
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs162560; hg19: chr2-38299515;