chr15-74756121-G-GTT

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -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
• Publications: 1 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000761.5. 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
	CYP1A2	NM_000761.5	MANE Select	c.*1046_*1047dupTT		3_prime_UTR	Exon 7 of 7	NP_000752.2	P05177

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP1A2	ENST00000343932.5	TSL:1 MANE Select	c.*1046_*1047dupTT		3_prime_UTR	Exon 7 of 7	ENSP00000342007.4	P05177
	CYP1A2	ENST00000872476.1		c.*1046_*1047dupTT		3_prime_UTR	Exon 7 of 7	ENSP00000542535.1
	CYP1A2	ENST00000872478.1		c.*1046_*1047dupTT		3_prime_UTR	Exon 7 of 7	ENSP00000542537.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 14

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.00345 AC: 115 AN: 33348

American (AMR) AF: 0.000466 AC: 6 AN: 12864

Ashkenazi Jewish (ASJ) AF: 0.00939 AC: 30 AN: 3194

East Asian (EAS) AF: 0.00 AC: 0 AN: 4370

South Asian (SAS) AF: 0.000744 AC: 3 AN: 4030

European-Finnish (FIN) AF: 0.000420 AC: 3 AN: 7146

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 242

European-Non Finnish (NFE) AF: 0.000195 AC: 12 AN: 61558

Other (OTH) AF: 0.00113 AC: 2 AN: 1776

Alfa AF: 0.00 Hom.: 443

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.25

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs34002060; hg19: chr15-75048462;