rs11636419

Positions:

• chr15-74755259-A-G
• chr15-74755259-A-T

Variant summary

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

The NM_000761.5(CYP1A2):​c.*171A>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 0.0875 in 775,572 control chromosomes in the GnomAD database, including 4,835 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 0.095 (932 hom., cov: 29)
  • Exomes 𝑓: 0.086 (3903 hom.)
• Consequence: CYP1A2 NM_000761.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.143

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 (SAS) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP1A2	NM_000761.5	c.*171A>G		3_prime_UTR_variant	7/7	ENST00000343932.5	NP_000752.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP1A2	ENST00000343932.5	c.*171A>G		3_prime_UTR_variant	7/7	1	NM_000761.5	ENSP00000342007.4

Frequencies

GnomAD3 genomes AF: 0.0953 AC: 14391 AN: 150984 Hom.: 920 Cov.: 29

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.0581

Gnomad AMR AF: 0.0768

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.228

Gnomad SAS AF: 0.295

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0532

Gnomad OTH AF: 0.0910

GnomAD4 exome AF: 0.0855 AC: 53409 AN: 624480 Hom.: 3903 Cov.: 9 AF XY: 0.0929 AC XY: 29381 AN XY: 316296

Gnomad4 AFR exome AF: 0.136

Gnomad4 AMR exome AF: 0.0763

Gnomad4 ASJ exome AF: 0.104

Gnomad4 EAS exome AF: 0.208

Gnomad4 SAS exome AF: 0.283

Gnomad4 FIN exome AF: 0.107

Gnomad4 NFE exome AF: 0.0525

Gnomad4 OTH exome AF: 0.101

GnomAD4 genome AF: 0.0955 AC: 14422 AN: 151092 Hom.: 932 Cov.: 29 AF XY: 0.102 AC XY: 7535 AN XY: 73756

Gnomad4 AFR AF: 0.130

Gnomad4 AMR AF: 0.0767

Gnomad4 ASJ AF: 0.103

Gnomad4 EAS AF: 0.227

Gnomad4 SAS AF: 0.296

Gnomad4 FIN AF: 0.107

Gnomad4 NFE AF: 0.0532

Gnomad4 OTH AF: 0.0982

Alfa AF: 0.0706 Hom.: 67

Bravo AF: 0.0893

Asia WGS AF: 0.306 AC: 1060 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.0
DANN	Benign	0.54

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: rs11636419; hg19: chr15-75047600; COSMIC: COSV59659448;