NM_000104.4:c.-2+129G>A

Variant names:

• chr2-38075651-C-T
• rs2551188
• NM_000104.4:c.-2+129G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000104.4(CYP1B1):​c.-2+129G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 573,238 control chromosomes in the GnomAD database, including 28,887 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.35 (9695 hom., cov: 34)
  • Exomes 𝑓: 0.29 (19192 hom.)
• Consequence: CYP1B1 NM_000104.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.170
• Publications: 23 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

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 2-38075651-C-T is Benign according to our data. Variant chr2-38075651-C-T is described in ClinVar as Benign. ClinVar VariationId is 1248456.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.467 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.-2+129G>A		intron	N/A	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.-2+129G>A		intron	N/A	ENSP00000478561.1	Q16678
	CYP1B1	ENST00000860003.1		c.-263G>A		5_prime_UTR	Exon 1 of 2	ENSP00000530062.1
	CYP1B1	ENST00000490576.2	TSL:4	c.-1-262G>A		intron	N/A	ENSP00000478839.2	Q16678

Frequencies

GnomAD3 genomes AF: 0.345 AC: 52459 AN: 152066 Hom.: 9675 Cov.: 34

Gnomad AFR AF: 0.472

Gnomad AMI AF: 0.503

Gnomad AMR AF: 0.318

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.381

Gnomad FIN AF: 0.367

Gnomad MID AF: 0.312

Gnomad NFE AF: 0.286

Gnomad OTH AF: 0.312

GnomAD4 exome AF: 0.294 AC: 123761 AN: 421056 Hom.: 19192 Cov.: 3 AF XY: 0.297 AC XY: 65660 AN XY: 221092

African (AFR) AF: 0.480 AC: 5680 AN: 11836

American (AMR) AF: 0.310 AC: 5467 AN: 17608

Ashkenazi Jewish (ASJ) AF: 0.229 AC: 2979 AN: 13000

East Asian (EAS) AF: 0.141 AC: 4080 AN: 28946

South Asian (SAS) AF: 0.365 AC: 15998 AN: 43882

European-Finnish (FIN) AF: 0.358 AC: 9735 AN: 27174

Middle Eastern (MID) AF: 0.319 AC: 588 AN: 1846

European-Non Finnish (NFE) AF: 0.285 AC: 71910 AN: 252270

Other (OTH) AF: 0.299 AC: 7324 AN: 24494

GnomAD4 genome AF: 0.345 AC: 52525 AN: 152182 Hom.: 9695 Cov.: 34 AF XY: 0.349 AC XY: 25975 AN XY: 74400

African (AFR) AF: 0.472 AC: 19598 AN: 41490

American (AMR) AF: 0.317 AC: 4851 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.214 AC: 742 AN: 3470

East Asian (EAS) AF: 0.181 AC: 937 AN: 5178

South Asian (SAS) AF: 0.381 AC: 1839 AN: 4826

European-Finnish (FIN) AF: 0.367 AC: 3884 AN: 10596

Middle Eastern (MID) AF: 0.295 AC: 86 AN: 292

European-Non Finnish (NFE) AF: 0.286 AC: 19458 AN: 68008

Other (OTH) AF: 0.318 AC: 672 AN: 2112

Alfa AF: 0.305 Hom.: 24751

Bravo AF: 0.342

Asia WGS AF: 0.312 AC: 1083 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	7.6
DANN	Benign	0.82
PhyloP100		-0.17
PromoterAI		-0.060	Neutral
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: rs2551188; hg19: chr2-38302794; COSMIC: COSV53190987; COSMIC: COSV53190987;