rs886038239

Variant names:

• chr2-38075792-G-A
• rs886038239
• NM_000104.4:c.-14C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_000104.4(CYP1B1):​c.-14C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). The gene CYP1B1 is included in the ClinGen Criteria Specification Registry.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CYP1B1 NM_000104.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0230
• Publications: 0 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

Specifications for CYP1B1 are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 2-38075792-G-A is Benign according to our data. Variant chr2-38075792-G-A is described in ClinVar as Benign. ClinVar VariationId is 255128.Status of the report is criteria_provided_single_submitter, 1 stars.

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.-14C>T		5_prime_UTR	Exon 1 of 3	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.-14C>T		5_prime_UTR	Exon 1 of 3	ENSP00000478561.1	Q16678
	CYP1B1	ENST00000614273.1	TSL:5	c.-18C>T		5_prime_UTR	Exon 1 of 3	ENSP00000483678.1	Q16678
	CYP1B1	ENST00000714520.1		c.-14C>T		5_prime_UTR	Exon 1 of 3	ENSP00000519767.1	Q16678

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 110702 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 58510

African (AFR) AF: 0.00 AC: 0 AN: 3088

American (AMR) AF: 0.00 AC: 0 AN: 4986

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2852

East Asian (EAS) AF: 0.00 AC: 0 AN: 5474

South Asian (SAS) AF: 0.00 AC: 0 AN: 15814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4666

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 424

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67542

Other (OTH) AF: 0.00 AC: 0 AN: 5856

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	12
DANN	Benign	0.85
PhyloP100		-0.023
PromoterAI		-0.062	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs886038239;

hg19: chr2-38302935;