chr15-74756121-G-GT

Variant names:

• chr15-74756121-G-GT
• rs34002060
• NM_000761.5:c.*1047dupT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_000761.5(CYP1A2):​c.*1047dupT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.046 (239 hom., cov: 0)
  • Exomes 𝑓: 0.14 (0 hom.)
• Consequence: CYP1A2 NM_000761.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.254

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP1A2	NM_000761.5	c.*1047dupT		3_prime_UTR_variant	Exon 7 of 7	ENST00000343932.5	NP_000752.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP1A2	ENST00000343932.5	c.*1047dupT		3_prime_UTR_variant	Exon 7 of 7	1	NM_000761.5	ENSP00000342007.4

Frequencies

GnomAD3 genomes AF: 0.0459 AC: 5934 AN: 129294 Hom.: 238 Cov.: 0

Gnomad AFR AF: 0.0194

Gnomad AMI AF: 0.0572

Gnomad AMR AF: 0.0492

Gnomad ASJ AF: 0.0768

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.212

Gnomad FIN AF: 0.0583

Gnomad MID AF: 0.0725

Gnomad NFE AF: 0.0376

Gnomad OTH AF: 0.0556

GnomAD4 exome AF: 0.143 AC: 2 AN: 14 Hom.: 0 Cov.: 0 AF XY: 0.125 AC XY: 1 AN XY: 8

Gnomad4 NFE exome AF: 0.143

GnomAD4 genome AF: 0.0459 AC: 5936 AN: 129296 Hom.: 239 Cov.: 0 AF XY: 0.0504 AC XY: 3133 AN XY: 62188

Gnomad4 AFR AF: 0.0194

Gnomad4 AMR AF: 0.0493

Gnomad4 ASJ AF: 0.0768

Gnomad4 EAS AF: 0.151

Gnomad4 SAS AF: 0.213

Gnomad4 FIN AF: 0.0583

Gnomad4 NFE AF: 0.0376

Gnomad4 OTH AF: 0.0576

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs34002060; hg19: chr15-75048462;