NM_000104.4:c.1043+275C>T

Variant names:

• chr2-38074071-G-A
• rs6759786
• NM_000104.4:c.1043+275C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_000104.4(CYP1B1):​c.1043+275C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00592 in 560,912 control chromosomes in the GnomAD database, including 57 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.015 (43 hom., cov: 33)
  • Exomes 𝑓: 0.0026 (14 hom.)
• Consequence: CYP1B1 NM_000104.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0890
• 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

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 2-38074071-G-A is Benign according to our data. Variant chr2-38074071-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1206581.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0148 (2246/152156) while in subpopulation AFR AF = 0.0479 (1989/41490). AF 95% confidence interval is 0.0462. There are 43 homozygotes in GnomAd4. There are 1080 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 43 AD,AR gene

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.1043+275C>T		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.1043+275C>T		intron	N/A	ENSP00000478561.1	Q16678
	CYP1B1	ENST00000490576.2	TSL:4	c.1043+275C>T		intron	N/A	ENSP00000478839.2	Q16678
	CYP1B1	ENST00000614273.1	TSL:5	c.1043+275C>T		intron	N/A	ENSP00000483678.1	Q16678

Frequencies

GnomAD3 genomes AF: 0.0147 AC: 2238 AN: 152038 Hom.: 42 Cov.: 33

Gnomad AFR AF: 0.0478

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00766

Gnomad ASJ AF: 0.00634

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.000660

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00109

Gnomad OTH AF: 0.0159

GnomAD4 exome AF: 0.00263 AC: 1073 AN: 408756 Hom.: 14 AF XY: 0.00243 AC XY: 519 AN XY: 213466

African (AFR) AF: 0.0472 AC: 558 AN: 11820

American (AMR) AF: 0.00520 AC: 86 AN: 16542

Ashkenazi Jewish (ASJ) AF: 0.00379 AC: 49 AN: 12914

East Asian (EAS) AF: 0.00 AC: 0 AN: 28304

South Asian (SAS) AF: 0.000235 AC: 9 AN: 38330

European-Finnish (FIN) AF: 0.000372 AC: 10 AN: 26860

Middle Eastern (MID) AF: 0.00978 AC: 18 AN: 1840

European-Non Finnish (NFE) AF: 0.000867 AC: 215 AN: 247990

Other (OTH) AF: 0.00530 AC: 128 AN: 24156

GnomAD4 genome AF: 0.0148 AC: 2246 AN: 152156 Hom.: 43 Cov.: 33 AF XY: 0.0145 AC XY: 1080 AN XY: 74376

African (AFR) AF: 0.0479 AC: 1989 AN: 41490

American (AMR) AF: 0.00758 AC: 116 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00634 AC: 22 AN: 3472

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5160

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4814

European-Finnish (FIN) AF: 0.000660 AC: 7 AN: 10608

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00109 AC: 74 AN: 67998

Other (OTH) AF: 0.0157 AC: 33 AN: 2104

Alfa AF: 0.0102 Hom.: 2

Bravo AF: 0.0169

Asia WGS AF: 0.00404 AC: 14 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	3.7
DANN	Benign	0.86
PhyloP100		-0.089
Mutation Taster		=100/0	polymorphism

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: rs6759786; hg19: chr2-38301214;