rs17861162

Variant names:

• chr15-74756412-C-G
• rs17861162
• NM_000761.5:c.*1324C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000761.5(CYP1A2):​c.*1324C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0993 in 152,114 control chromosomes in the GnomAD database, including 1,034 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.099 (1034 hom., cov: 31)
• Consequence: CYP1A2 NM_000761.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.261
• Publications: 9 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP1A2	NM_000761.5	c.*1324C>G		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.*1324C>G		3_prime_UTR_variant	Exon 7 of 7	1	NM_000761.5	ENSP00000342007.4

Frequencies

GnomAD3 genomes AF: 0.0991 AC: 15070 AN: 151996 Hom.: 1017 Cov.: 31

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.0757

Gnomad AMR AF: 0.0828

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.223

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.0983

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0546

Gnomad OTH AF: 0.0990

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0993 AC: 15112 AN: 152114 Hom.: 1034 Cov.: 31 AF XY: 0.106 AC XY: 7863 AN XY: 74334

African (AFR) AF: 0.139 AC: 5767 AN: 41476

American (AMR) AF: 0.0828 AC: 1265 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.121 AC: 419 AN: 3468

East Asian (EAS) AF: 0.223 AC: 1155 AN: 5170

South Asian (SAS) AF: 0.296 AC: 1426 AN: 4820

European-Finnish (FIN) AF: 0.0983 AC: 1039 AN: 10574

Middle Eastern (MID) AF: 0.123 AC: 36 AN: 292

European-Non Finnish (NFE) AF: 0.0546 AC: 3710 AN: 68006

Other (OTH) AF: 0.107 AC: 226 AN: 2112

Alfa AF: 0.0778 Hom.: 73

Bravo AF: 0.0944

Asia WGS AF: 0.304 AC: 1056 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.1
DANN	Benign	0.39
PhyloP100		0.26

Splicing

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

Other links and lift over

dbSNP: rs17861162; hg19: chr15-75048753;