2-38071734-T-G

Variant names:

• chr2-38071734-T-G
• rs162561
• NM_000104.4:c.1044-424A>C

Variant summary

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

The NM_000104.4(CYP1B1):​c.1044-424A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.849 in 152,122 control chromosomes in the GnomAD database, including 54,967 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 0.85 (54967 hom., cov: 33)
• Consequence: CYP1B1 NM_000104.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33
• Publications: 15 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: ClinGen, Ambry Genetics
• glaucoma 3A

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, G2P
• anterior segment dysgenesis 6

  Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia
• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.909 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP1B1	NM_000104.4	c.1044-424A>C		intron_variant	Intron 2 of 2	ENST00000610745.5	NP_000095.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP1B1	ENST00000610745.5	c.1044-424A>C		intron_variant	Intron 2 of 2	1	NM_000104.4	ENSP00000478561.1

Frequencies

GnomAD3 genomes AF: 0.849 AC: 129028 AN: 152004 Hom.: 54920 Cov.: 33

Gnomad AFR AF: 0.871

Gnomad AMI AF: 0.784

Gnomad AMR AF: 0.918

Gnomad ASJ AF: 0.830

Gnomad EAS AF: 0.922

Gnomad SAS AF: 0.932

Gnomad FIN AF: 0.795

Gnomad MID AF: 0.949

Gnomad NFE AF: 0.817

Gnomad OTH AF: 0.878

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

GnomAD4 genome AF: 0.849 AC: 129136 AN: 152122 Hom.: 54967 Cov.: 33 AF XY: 0.851 AC XY: 63267 AN XY: 74370

African (AFR) AF: 0.871 AC: 36135 AN: 41502

American (AMR) AF: 0.918 AC: 14032 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.830 AC: 2880 AN: 3468

East Asian (EAS) AF: 0.921 AC: 4771 AN: 5178

South Asian (SAS) AF: 0.932 AC: 4490 AN: 4820

European-Finnish (FIN) AF: 0.795 AC: 8401 AN: 10564

Middle Eastern (MID) AF: 0.949 AC: 279 AN: 294

European-Non Finnish (NFE) AF: 0.817 AC: 55574 AN: 67986

Other (OTH) AF: 0.879 AC: 1859 AN: 2114

Alfa AF: 0.837 Hom.: 63808

Bravo AF: 0.860

Asia WGS AF: 0.923 AC: 3210 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.4
DANN	Benign	0.77
PhyloP100		-1.3
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: rs162561; hg19: chr2-38298877;