rs2472304

Variant names:

• chr15-74751897-G-A
• rs2472304
• NM_000761.5:c.1042+43G>A

Your query was ambiguous. Multiple possible variants found:

• chr15-74751897-G-A
• chr15-74751897-G-C
• chr15-74751897-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 110 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=-0.89).
• 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 rank	MANE	Protein	UniProt
CYP1A2	NM_000761.5	c.1042+43G>A		intron_variant	Intron 4 of 6	ENST00000343932.5	NP_000752.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP1A2	ENST00000343932.5	c.1042+43G>A		intron_variant	Intron 4 of 6	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

GnomAD2 exomes AF: 0.457 AC: 111309 AN: 243628 AF XY: 0.462

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 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

African (AFR) AF: 0.106 AC: 3481 AN: 32872

American (AMR) AF: 0.274 AC: 11761 AN: 42970

Ashkenazi Jewish (ASJ) AF: 0.554 AC: 14127 AN: 25520

East Asian (EAS) AF: 0.186 AC: 7363 AN: 39632

South Asian (SAS) AF: 0.209 AC: 17817 AN: 85110

European-Finnish (FIN) AF: 0.566 AC: 30116 AN: 53254

Middle Eastern (MID) AF: 0.506 AC: 2843 AN: 5622

European-Non Finnish (NFE) AF: 0.662 AC: 730117 AN: 1102932

Other (OTH) AF: 0.540 AC: 32259 AN: 59756

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

African (AFR) AF: 0.123 AC: 5120 AN: 41484

American (AMR) AF: 0.352 AC: 5375 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.549 AC: 1906 AN: 3470

East Asian (EAS) AF: 0.155 AC: 803 AN: 5172

South Asian (SAS) AF: 0.191 AC: 919 AN: 4814

European-Finnish (FIN) AF: 0.558 AC: 5899 AN: 10564

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.647 AC: 43961 AN: 67944

Other (OTH) AF: 0.444 AC: 935 AN: 2106

Alfa AF: 0.581 Hom.: 118598

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
PhyloP100		-0.13
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2472304; hg19: chr15-75044238; COSMIC: COSV59659887;