rs9341247

Variant names:

• chr2-38074825-G-T
• rs9341247
• NM_000104.4:c.564C>A

Your query was ambiguous. Multiple possible variants found:

• chr2-38074825-G-T
• chr2-38074825-G-A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000104.4(CYP1B1):​c.564C>A​(p.Gly188Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00412 in 1,567,192 control chromosomes in the GnomAD database, including 239 homozygotes. 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: 𝑓 0.022 (123 hom., cov: 33)
  • Exomes 𝑓: 0.0022 (116 hom.)
• Consequence: CYP1B1 NM_000104.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -1.06
• Publications: 10 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: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 2-38074825-G-T is Benign according to our data. Variant chr2-38074825-G-T is described in ClinVar as Benign. ClinVar VariationId is 166973.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.06 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0755 is higher than 0.05.

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.564C>A	p.Gly188Gly	synonymous	Exon 2 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.564C>A	p.Gly188Gly	synonymous	Exon 2 of 3	ENSP00000478561.1	Q16678
	CYP1B1	ENST00000490576.2	TSL:4	c.564C>A	p.Gly188Gly	synonymous	Exon 2 of 3	ENSP00000478839.2	Q16678
	CYP1B1	ENST00000614273.1	TSL:5	c.564C>A	p.Gly188Gly	synonymous	Exon 2 of 3	ENSP00000483678.1	Q16678

Frequencies

GnomAD3 genomes AF: 0.0223 AC: 3395 AN: 152206 Hom.: 124 Cov.: 33

Gnomad AFR AF: 0.0779

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00746

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00321

Gnomad NFE AF: 0.000367

Gnomad OTH AF: 0.0129

GnomAD2 exomes AF: 0.00489 AC: 793 AN: 162086 AF XY: 0.00364

Gnomad AFR exome AF: 0.0811

Gnomad AMR exome AF: 0.00367

Gnomad ASJ exome AF: 0.000126

Gnomad EAS exome AF: 0.0000804

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000224

Gnomad OTH exome AF: 0.000676

GnomAD4 exome AF: 0.00216 AC: 3062 AN: 1414868 Hom.: 116 Cov.: 31 AF XY: 0.00180 AC XY: 1259 AN XY: 699656

African (AFR) AF: 0.0781 AC: 2533 AN: 32434

American (AMR) AF: 0.00416 AC: 159 AN: 38238

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24990

East Asian (EAS) AF: 0.00 AC: 0 AN: 37082

South Asian (SAS) AF: 0.0000742 AC: 6 AN: 80898

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48498

Middle Eastern (MID) AF: 0.00279 AC: 15 AN: 5372

European-Non Finnish (NFE) AF: 0.0000873 AC: 95 AN: 1088822

Other (OTH) AF: 0.00434 AC: 254 AN: 58534

GnomAD4 genome AF: 0.0223 AC: 3397 AN: 152324 Hom.: 123 Cov.: 33 AF XY: 0.0220 AC XY: 1638 AN XY: 74496

African (AFR) AF: 0.0777 AC: 3230 AN: 41564

American (AMR) AF: 0.00745 AC: 114 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00345 AC: 1 AN: 290

European-Non Finnish (NFE) AF: 0.000367 AC: 25 AN: 68030

Other (OTH) AF: 0.0128 AC: 27 AN: 2114

Alfa AF: 0.00265 Hom.: 6

Bravo AF: 0.0254

Asia WGS AF: 0.00404 AC: 14 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	1	Congenital glaucoma (1)
-	-	1	Glaucoma 3A (1)
-	-	1	Irido-corneo-trabecular dysgenesis (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.7
DANN	Benign	0.84
PhyloP100		-1.1
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: rs9341247; hg19: chr2-38301968;