chr2-38074660-C-G

Variant names:

• chr2-38074660-C-G
• rs9341249
• NM_000104.4:c.729G>C

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_000104.4(CYP1B1):​c.729G>C​(p.Val243Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0126 in 1,613,280 control chromosomes in the GnomAD database, including 1,870 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.064 (1009 hom., cov: 33)
  • Exomes 𝑓: 0.0073 (861 hom.)
• Consequence: CYP1B1 NM_000104.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.501

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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 2-38074660-C-G is Benign according to our data. Variant chr2-38074660-C-G is described in ClinVar as [Benign]. Clinvar id is 166972.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-38074660-C-G is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-0.501 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP1B1	NM_000104.4	c.729G>C	p.Val243Val	synonymous_variant	Exon 2 of 3	ENST00000610745.5	NP_000095.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP1B1	ENST00000610745.5	c.729G>C	p.Val243Val	synonymous_variant	Exon 2 of 3	1	NM_000104.4	ENSP00000478561.1

Frequencies

GnomAD3 genomes AF: 0.0638 AC: 9716 AN: 152210 Hom.: 1003 Cov.: 33

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0218

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.00943

Gnomad SAS AF: 0.00310

Gnomad FIN AF: 0.000753

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00151

Gnomad OTH AF: 0.0464

GnomAD3 exomes AF: 0.0179 AC: 4425 AN: 247312 Hom.: 381 AF XY: 0.0131 AC XY: 1762 AN XY: 134388

Gnomad AFR exome AF: 0.221

Gnomad AMR exome AF: 0.0128

Gnomad ASJ exome AF: 0.00502

Gnomad EAS exome AF: 0.00983

Gnomad SAS exome AF: 0.00141

Gnomad FIN exome AF: 0.000512

Gnomad NFE exome AF: 0.00139

Gnomad OTH exome AF: 0.00891

GnomAD4 exome AF: 0.00728 AC: 10635 AN: 1460952 Hom.: 861 Cov.: 31 AF XY: 0.00644 AC XY: 4682 AN XY: 726766

Gnomad4 AFR exome AF: 0.221

Gnomad4 AMR exome AF: 0.0137

Gnomad4 ASJ exome AF: 0.00379

Gnomad4 EAS exome AF: 0.00882

Gnomad4 SAS exome AF: 0.00139

Gnomad4 FIN exome AF: 0.000456

Gnomad4 NFE exome AF: 0.000860

Gnomad4 OTH exome AF: 0.0163

GnomAD4 genome AF: 0.0640 AC: 9746 AN: 152328 Hom.: 1009 Cov.: 33 AF XY: 0.0614 AC XY: 4576 AN XY: 74484

Gnomad4 AFR AF: 0.220

Gnomad4 AMR AF: 0.0217

Gnomad4 ASJ AF: 0.00461

Gnomad4 EAS AF: 0.00946

Gnomad4 SAS AF: 0.00290

Gnomad4 FIN AF: 0.000753

Gnomad4 NFE AF: 0.00151

Gnomad4 OTH AF: 0.0459

Alfa AF: 0.0183 Hom.: 73

Bravo AF: 0.0722

Asia WGS AF: 0.0220 AC: 76 AN: 3478

EpiCase AF: 0.00125

EpiControl AF: 0.00219

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1

Apr 24, 2014

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Glaucoma 3A Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Irido-corneo-trabecular dysgenesis Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Congenital glaucoma Benign:1

Jan 23, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	9.3
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: rs9341249; hg19: chr2-38301803;