15-74756121-GTTT-GTT

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_000761.5(CYP1A2):​c.*1047delT 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 0.42 (13305 hom., cov: 0)
  • Exomes 𝑓: 0.43 (0 hom.)
• 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: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.597 is higher than 0.05.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.423 AC: 54646 AN: 129138 Hom.: 13314 Cov.: 0

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.440

Gnomad AMR AF: 0.353

Gnomad ASJ AF: 0.530

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.517

Gnomad MID AF: 0.523

Gnomad NFE AF: 0.603

Gnomad OTH AF: 0.426

GnomAD4 exome AF: 0.429 AC: 6 AN: 14 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 4 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: 0.429 AC: 6 AN: 14

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.423 AC: 54617 AN: 129138 Hom.: 13305 Cov.: 0 AF XY: 0.409 AC XY: 25397 AN XY: 62136

African (AFR) AF: 0.149 AC: 4963 AN: 33316

American (AMR) AF: 0.353 AC: 4533 AN: 12854

Ashkenazi Jewish (ASJ) AF: 0.530 AC: 1687 AN: 3184

East Asian (EAS) AF: 0.162 AC: 706 AN: 4368

South Asian (SAS) AF: 0.198 AC: 796 AN: 4026

European-Finnish (FIN) AF: 0.517 AC: 3696 AN: 7144

Middle Eastern (MID) AF: 0.525 AC: 127 AN: 242

European-Non Finnish (NFE) AF: 0.602 AC: 36999 AN: 61414

Other (OTH) AF: 0.423 AC: 748 AN: 1768

Alfa AF: 0.222 Hom.: 443

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.25
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs34002060; hg19: chr15-75048462;