2-38071060-G-C

Position:

• chr2-38071060-G-C

Variant summary

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

The NM_000104.4(CYP1B1):​c.1294C>G​(p.Leu432Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.425 in 1,613,386 control chromosomes in the GnomAD database, including 156,236 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/6 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.49 (21268 hom., cov: 32)
  • Exomes 𝑓: 0.42 (134968 hom.)
• Consequence: CYP1B1 NM_000104.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.334

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005228162).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.767 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP1B1	NM_000104.4	c.1294C>G	p.Leu432Val	missense_variant	3/3	ENST00000610745.5	NP_000095.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP1B1	ENST00000610745.5	c.1294C>G	p.Leu432Val	missense_variant	3/3	1	NM_000104.4	ENSP00000478561.1

Frequencies

GnomAD3 genomes AF: 0.492 AC: 74816 AN: 151976 Hom.: 21223 Cov.: 32

Gnomad AFR AF: 0.774

Gnomad AMI AF: 0.357

Gnomad AMR AF: 0.318

Gnomad ASJ AF: 0.516

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.360

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.433

Gnomad OTH AF: 0.446

GnomAD4 exome AF: 0.418 AC: 610248 AN: 1461292 Hom.: 134968 Cov.: 64 AF XY: 0.411 AC XY: 298608 AN XY: 726824

Gnomad4 AFR exome AF: 0.782

Gnomad4 AMR exome AF: 0.230

Gnomad4 ASJ exome AF: 0.493

Gnomad4 EAS exome AF: 0.125

Gnomad4 SAS exome AF: 0.220

Gnomad4 FIN exome AF: 0.367

Gnomad4 NFE exome AF: 0.441

Gnomad4 OTH exome AF: 0.411

GnomAD4 genome AF: 0.493 AC: 74925 AN: 152094 Hom.: 21268 Cov.: 32 AF XY: 0.479 AC XY: 35574 AN XY: 74344

Gnomad4 AFR AF: 0.774

Gnomad4 AMR AF: 0.317

Gnomad4 ASJ AF: 0.516

Gnomad4 EAS AF: 0.113

Gnomad4 SAS AF: 0.200

Gnomad4 FIN AF: 0.360

Gnomad4 NFE AF: 0.433

Gnomad4 OTH AF: 0.443

Alfa AF: 0.421 Hom.: 10147

Bravo AF: 0.503

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Mendelics

May 04, 2022

- -

Congenital glaucoma Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_noAF	Benign	-0.61
CADD	Benign	8.9
DEOGEN2	Benign	0.077	T;T;T
LIST_S2	Benign	0.034	.;T;T
MetaRNN	Benign	0.0052	T;T;T
Sift4G	Benign	0.29	T;T;T
Vest4		0.053
gMVP		0.69

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1056836; hg19: chr2-38298203;