rs34002060

chr15-74756121-GTT-Gchr15-74756121-GTT-GTchr15-74756121-GTT-GTTTchr15-74756121-GTT-GTTTTchr15-74756121-GTT-GTTTTTchr15-74756121-GTT-GTTTTTTTTTTT

Variant summary

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

The NM_000761.5(CYP1A2):c.*1046_*1047del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000201 in 129,352 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00019 (0 hom., cov: 0)
  • Exomes 𝑓: 0.071 (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: GnomAdExome4 highest subpopulation (NFE) allele frequency = 0.0714 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP1A2	NM_000761.5	c.*1046_*1047del		3_prime_UTR_variant	7/7	ENST00000343932.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP1A2	ENST00000343932.5	c.*1046_*1047del		3_prime_UTR_variant	7/7	1	NM_000761.5	P1

Frequencies

GnomAD3 genomes AF: 0.000193 AC: 25 AN: 129336 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000300

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000233

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000980

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000227

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0714 AC: 1 AN: 14 Hom.: 0 AF XY: 0.125 AC XY: 1 AN XY: 8

Gnomad4 NFE exome AF: 0.0714

GnomAD4 genome AF: 0.000193 AC: 25 AN: 129338 Hom.: 0 Cov.: 0 AF XY: 0.000161 AC XY: 10 AN XY: 62222

Gnomad4 AFR AF: 0.0000300

Gnomad4 AMR AF: 0.000233

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000980

Gnomad4 NFE AF: 0.000227

Gnomad4 OTH AF: 0.00

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;