chr15-74749000-T-G

Variant names:

• chr15-74749000-T-G
• rs2069526
• NM_000761.5:c.-10+103T>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.-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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.054 (331 hom., cov: 32)
  • Exomes 𝑓: 0.019 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CYP1A2 NM_000761.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.702
• Publications: 51 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000761.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP1A2	NM_000761.5	MANE Select	c.-10+103T>G		intron	N/A	NP_000752.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP1A2	ENST00000343932.5	TSL:1 MANE Select	c.-10+103T>G		intron	N/A	ENSP00000342007.4

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

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.00 AC: 0 AN: 2

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: 0.0200 AC: 1 AN: 50

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.107 AC: 4437 AN: 41470

American (AMR) AF: 0.0353 AC: 540 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0576 AC: 200 AN: 3470

East Asian (EAS) AF: 0.0787 AC: 408 AN: 5184

South Asian (SAS) AF: 0.0867 AC: 417 AN: 4812

European-Finnish (FIN) AF: 0.0486 AC: 515 AN: 10590

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0222 AC: 1512 AN: 68000

Other (OTH) AF: 0.0458 AC: 97 AN: 2116

Alfa AF: 0.0324 Hom.: 471

Bravo AF: 0.0533

Asia WGS AF: 0.0730 AC: 254 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	6.5
DANN	Benign	0.68
PhyloP100		0.70
PromoterAI		0.024	Neutral
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: rs2069526; hg19: chr15-75041341;