rs2069526

Positions:

• chr15-74749000-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000343932.5(CYP1A2):​c.-10+103T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0537 in 152,126 control chromosomes in the GnomAD database, including 331 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.054 (331 hom., cov: 32)
  • Exomes 𝑓: 0.019 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CYP1A2 ENST00000343932.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.702

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP1A2	NM_000761.5	c.-10+103T>G		intron_variant		ENST00000343932.5	NP_000752.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP1A2	ENST00000343932.5	c.-10+103T>G		intron_variant		1	NM_000761.5	ENSP00000342007	P1

Frequencies

GnomAD3 genomes AF: 0.0537 AC: 8169 AN: 152008 Hom.: 332 Cov.: 32

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.0231

Gnomad AMR AF: 0.0354

Gnomad ASJ AF: 0.0576

Gnomad EAS AF: 0.0795

Gnomad SAS AF: 0.0860

Gnomad FIN AF: 0.0486

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0222

Gnomad OTH AF: 0.0463

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0192 AC: 1 AN: 52 Hom.: 0 AF XY: 0.0250 AC XY: 1 AN XY: 40

Gnomad4 AMR exome AF: 0.00

Gnomad4 NFE exome AF: 0.0200

GnomAD4 genome AF: 0.0537 AC: 8166 AN: 152126 Hom.: 331 Cov.: 32 AF XY: 0.0551 AC XY: 4098 AN XY: 74384

Gnomad4 AFR AF: 0.107

Gnomad4 AMR AF: 0.0353

Gnomad4 ASJ AF: 0.0576

Gnomad4 EAS AF: 0.0787

Gnomad4 SAS AF: 0.0867

Gnomad4 FIN AF: 0.0486

Gnomad4 NFE AF: 0.0222

Gnomad4 OTH AF: 0.0458

Alfa AF: 0.0295 Hom.: 147

Bravo AF: 0.0533

Asia WGS AF: 0.0730 AC: 254 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	6.5
DANN	Benign	0.68

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

Publications

LitVar

Other links and lift over

dbSNP: rs2069526; hg19: chr15-75041341;