2-38076937-T-C

Position:

• chr2-38076937-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000494864.1(CYP1B1):​c.-70-5627A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 152,138 control chromosomes in the GnomAD database, including 2,539 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 (2539 hom., cov: 33)
• Consequence: CYP1B1 ENST00000494864.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.32

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.38076937T>C		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP1B1	ENST00000494864.1	c.-70-5627A>G		intron_variant		5		ENSP00000479876.1
CYP1B1-AS1	ENST00000589303.5	n.281+377T>C		intron_variant		5
CYP1B1-AS1	ENST00000620177.4	n.421+869T>C		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.178 AC: 27083 AN: 152030 Hom.: 2539 Cov.: 33

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.0614

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.201

Gnomad EAS AF: 0.0190

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.201

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.192

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

GnomAD4 genome AF: 0.178 AC: 27105 AN: 152138 Hom.: 2539 Cov.: 33 AF XY: 0.171 AC XY: 12704 AN XY: 74382

Gnomad4 AFR AF: 0.195

Gnomad4 AMR AF: 0.156

Gnomad4 ASJ AF: 0.201

Gnomad4 EAS AF: 0.0190

Gnomad4 SAS AF: 0.105

Gnomad4 FIN AF: 0.115

Gnomad4 NFE AF: 0.200

Gnomad4 OTH AF: 0.190

Alfa AF: 0.185 Hom.: 362

Bravo AF: 0.185

Asia WGS AF: 0.0770 AC: 269 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	13
DANN	Benign	0.50

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs162558; hg19: chr2-38304079;