chr15-74756121-G-GTT

Variant names:

• chr15-74756121-G-GTT
• rs34002060
• NM_000761.5:c.*1046_*1047dupTT

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_000761.5(CYP1A2):​c.*1046_*1047dupTT 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 0.0013 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• 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 Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd4 at 171 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP1A2	NM_000761.5	c.*1046_*1047dupTT		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.*1046_*1047dupTT		3_prime_UTR_variant	Exon 7 of 7	1	NM_000761.5	ENSP00000342007.4

Frequencies

GnomAD3 genomes AF: 0.00131 AC: 169 AN: 129348 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00342

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000389

Gnomad ASJ AF: 0.00939

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000739

Gnomad FIN AF: 0.000420

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000195

Gnomad OTH AF: 0.00113

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 14 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 8

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.00132 AC: 171 AN: 129350 Hom.: 0 Cov.: 0 AF XY: 0.00130 AC XY: 81 AN XY: 62218

Gnomad4 AFR AF: 0.00345

Gnomad4 AMR AF: 0.000466

Gnomad4 ASJ AF: 0.00939

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000744

Gnomad4 FIN AF: 0.000420

Gnomad4 NFE AF: 0.000195

Gnomad4 OTH AF: 0.00113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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;