2-38079793-C-T

Variant names:

• chr2-38079793-C-T
• rs4646429
• ENST00000948951.1:c.-2+4156G>A

Variant summary

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

The ENST00000948951.1(CYP1B1):​c.-2+4156G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 152,120 control chromosomes in the GnomAD database, including 5,459 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 0.26 (5459 hom., cov: 32)
• Consequence: CYP1B1 ENST00000948951.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.61
• Publications: 12 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.353 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000948951.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP1B1	ENST00000948951.1		c.-2+4156G>A		intron	N/A	ENSP00000619010.1
	CYP1B1	ENST00000494864.1	TSL:5	c.-70-8483G>A		intron	N/A	ENSP00000479876.1	A0A087WW26
	CYP1B1-AS1	ENST00000589303.6	TSL:5	n.310+3233C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39170 AN: 152002 Hom.: 5461 Cov.: 32

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.504

Gnomad AMR AF: 0.287

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.171

Gnomad SAS AF: 0.367

Gnomad FIN AF: 0.368

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.285

Gnomad OTH AF: 0.249

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

GnomAD4 genome AF: 0.257 AC: 39164 AN: 152120 Hom.: 5459 Cov.: 32 AF XY: 0.265 AC XY: 19686 AN XY: 74358

African (AFR) AF: 0.171 AC: 7091 AN: 41506

American (AMR) AF: 0.286 AC: 4376 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.210 AC: 730 AN: 3470

East Asian (EAS) AF: 0.171 AC: 884 AN: 5176

South Asian (SAS) AF: 0.367 AC: 1773 AN: 4828

European-Finnish (FIN) AF: 0.368 AC: 3876 AN: 10542

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.285 AC: 19363 AN: 67990

Other (OTH) AF: 0.254 AC: 536 AN: 2114

Alfa AF: 0.269 Hom.: 9603

Bravo AF: 0.242

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.0
DANN	Benign	0.79
PhyloP100		-1.6

Splicing

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

Other links and lift over

dbSNP: rs4646429; hg19: chr2-38306935;