15-74752059-G-C

Position:

• chr15-74752059-G-C

Variant summary

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

The NM_000761.5(CYP1A2):​c.1043-65G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0432 in 1,603,436 control chromosomes in the GnomAD database, including 3,192 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.041 (259 hom., cov: 32)
  • Exomes 𝑓: 0.043 (2933 hom.)
• Consequence: CYP1A2 NM_000761.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.45

Genes affected

CYP1A2 (HGNC:2596): (cytochrome P450 family 1 subfamily A member 2) 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 protein encoded by this gene localizes to the endoplasmic reticulum and its expression is induced by some polycyclic aromatic hydrocarbons (PAHs), some of which are found in cigarette smoke. The enzyme's endogenous substrate is unknown; however, it is able to metabolize some PAHs to carcinogenic intermediates. Other xenobiotic substrates for this enzyme include caffeine, aflatoxin B1, and acetaminophen. The transcript from this gene contains four Alu sequences flanked by direct repeats in the 3' untranslated region. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.196 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP1A2	NM_000761.5	c.1043-65G>C		intron_variant		ENST00000343932.5	NP_000752.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP1A2	ENST00000343932.5	c.1043-65G>C		intron_variant		1	NM_000761.5	ENSP00000342007.4

Frequencies

GnomAD3 genomes AF: 0.0408 AC: 6201 AN: 152132 Hom.: 254 Cov.: 32

Gnomad AFR AF: 0.0291

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.0408

Gnomad ASJ AF: 0.0435

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.0326

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0289

Gnomad OTH AF: 0.0440

GnomAD4 exome AF: 0.0435 AC: 63122 AN: 1451186 Hom.: 2933 Cov.: 31 AF XY: 0.0476 AC XY: 34310 AN XY: 721234

Gnomad4 AFR exome AF: 0.0255

Gnomad4 AMR exome AF: 0.0416

Gnomad4 ASJ exome AF: 0.0409

Gnomad4 EAS exome AF: 0.149

Gnomad4 SAS exome AF: 0.187

Gnomad4 FIN exome AF: 0.0305

Gnomad4 NFE exome AF: 0.0293

Gnomad4 OTH exome AF: 0.0571

GnomAD4 genome AF: 0.0409 AC: 6224 AN: 152250 Hom.: 259 Cov.: 32 AF XY: 0.0448 AC XY: 3336 AN XY: 74452

Gnomad4 AFR AF: 0.0291

Gnomad4 AMR AF: 0.0409

Gnomad4 ASJ AF: 0.0435

Gnomad4 EAS AF: 0.152

Gnomad4 SAS AF: 0.207

Gnomad4 FIN AF: 0.0326

Gnomad4 NFE AF: 0.0289

Gnomad4 OTH AF: 0.0511

Alfa AF: 0.0158 Hom.: 11

Bravo AF: 0.0369

Asia WGS AF: 0.235 AC: 814 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.0050
DANN	Benign	0.63

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: rs3743484; hg19: chr15-75044400; COSMIC: COSV59659305;