2-38074071-G-A

Position:

• chr2-38074071-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The ENST00000610745.5(CYP1B1):​c.1043+275C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00592 in 560,912 control chromosomes in the GnomAD database, including 57 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.015 (43 hom., cov: 33)
  • Exomes 𝑓: 0.0026 (14 hom.)
• Consequence: CYP1B1 ENST00000610745.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0890

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

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 2-38074071-G-A is Benign according to our data. Variant chr2-38074071-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1206581.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0148 (2246/152156) while in subpopulation AFR AF= 0.0479 (1989/41490). AF 95% confidence interval is 0.0462. There are 43 homozygotes in gnomad4. There are 1080 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 43 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP1B1	NM_000104.4	c.1043+275C>T		intron_variant		ENST00000610745.5	NP_000095.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP1B1	ENST00000610745.5	c.1043+275C>T		intron_variant		1	NM_000104.4	ENSP00000478561	P1

Frequencies

GnomAD3 genomes AF: 0.0147 AC: 2238 AN: 152038 Hom.: 42 Cov.: 33

Gnomad AFR AF: 0.0478

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00766

Gnomad ASJ AF: 0.00634

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.000660

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00109

Gnomad OTH AF: 0.0159

GnomAD4 exome AF: 0.00263 AC: 1073 AN: 408756 Hom.: 14 AF XY: 0.00243 AC XY: 519 AN XY: 213466

Gnomad4 AFR exome AF: 0.0472

Gnomad4 AMR exome AF: 0.00520

Gnomad4 ASJ exome AF: 0.00379

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000235

Gnomad4 FIN exome AF: 0.000372

Gnomad4 NFE exome AF: 0.000867

Gnomad4 OTH exome AF: 0.00530

GnomAD4 genome AF: 0.0148 AC: 2246 AN: 152156 Hom.: 43 Cov.: 33 AF XY: 0.0145 AC XY: 1080 AN XY: 74376

Gnomad4 AFR AF: 0.0479

Gnomad4 AMR AF: 0.00758

Gnomad4 ASJ AF: 0.00634

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.000660

Gnomad4 NFE AF: 0.00109

Gnomad4 OTH AF: 0.0157

Alfa AF: 0.00868 Hom.: 2

Bravo AF: 0.0169

Asia WGS AF: 0.00404 AC: 14 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

May 25, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	3.7
DANN	Benign	0.86

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

Publications

LitVar

Other links and lift over

dbSNP: rs6759786; hg19: chr2-38301214;