rs2472304

Positions:

• chr15-74751897-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_000761.5(CYP1A2):​c.1042+43G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.572 in 1,599,708 control chromosomes in the GnomAD database, including 287,490 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.43 (18361 hom., cov: 32)
  • Exomes 𝑓: 0.59 (269129 hom.)
• Consequence: CYP1A2 NM_000761.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.129

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 15-74751897-G-A is Benign according to our data. Variant chr15-74751897-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.642 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP1A2	NM_000761.5	c.1042+43G>A		intron_variant		ENST00000343932.5	NP_000752.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP1A2	ENST00000343932.5	c.1042+43G>A		intron_variant		1	NM_000761.5	ENSP00000342007.4

Frequencies

GnomAD3 genomes AF: 0.431 AC: 65508 AN: 151922 Hom.: 18368 Cov.: 32

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.454

Gnomad AMR AF: 0.352

Gnomad ASJ AF: 0.549

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.558

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.647

Gnomad OTH AF: 0.449

GnomAD3 exomes AF: 0.457 AC: 111309 AN: 243628 Hom.: 31276 AF XY: 0.462 AC XY: 60983 AN XY: 131964

Gnomad AFR exome AF: 0.110

Gnomad AMR exome AF: 0.259

Gnomad ASJ exome AF: 0.561

Gnomad EAS exome AF: 0.157

Gnomad SAS exome AF: 0.203

Gnomad FIN exome AF: 0.565

Gnomad NFE exome AF: 0.650

Gnomad OTH exome AF: 0.531

GnomAD4 exome AF: 0.587 AC: 849884 AN: 1447668 Hom.: 269129 Cov.: 28 AF XY: 0.578 AC XY: 416499 AN XY: 720898

Gnomad4 AFR exome AF: 0.106

Gnomad4 AMR exome AF: 0.274

Gnomad4 ASJ exome AF: 0.554

Gnomad4 EAS exome AF: 0.186

Gnomad4 SAS exome AF: 0.209

Gnomad4 FIN exome AF: 0.566

Gnomad4 NFE exome AF: 0.662

Gnomad4 OTH exome AF: 0.540

GnomAD4 genome AF: 0.431 AC: 65490 AN: 152040 Hom.: 18361 Cov.: 32 AF XY: 0.418 AC XY: 31048 AN XY: 74310

Gnomad4 AFR AF: 0.123

Gnomad4 AMR AF: 0.352

Gnomad4 ASJ AF: 0.549

Gnomad4 EAS AF: 0.155

Gnomad4 SAS AF: 0.191

Gnomad4 FIN AF: 0.558

Gnomad4 NFE AF: 0.647

Gnomad4 OTH AF: 0.444

Alfa AF: 0.596 Hom.: 61905

Bravo AF: 0.410

Asia WGS AF: 0.157 AC: 552 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.6
DANN	Benign	0.39

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs2472304; hg19: chr15-75044238; COSMIC: COSV59659887;