rs11636419

Variant names:

• chr15-74755259-A-G
• rs11636419
• NM_000761.5:c.*171A>G

Your query was ambiguous. Multiple possible variants found:

• chr15-74755259-A-G
• chr15-74755259-A-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.*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
• Publications: 12 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 (SAS) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP1A2	NM_000761.5	c.*171A>G		3_prime_UTR_variant	Exon 7 of 7	ENST00000343932.5	NP_000752.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP1A2	ENST00000343932.5	c.*171A>G		3_prime_UTR_variant	Exon 7 of 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

African (AFR) AF: 0.136 AC: 2183 AN: 16020

American (AMR) AF: 0.0763 AC: 1334 AN: 17490

Ashkenazi Jewish (ASJ) AF: 0.104 AC: 1472 AN: 14154

East Asian (EAS) AF: 0.208 AC: 6262 AN: 30122

South Asian (SAS) AF: 0.283 AC: 12758 AN: 45056

European-Finnish (FIN) AF: 0.107 AC: 2892 AN: 27034

Middle Eastern (MID) AF: 0.0928 AC: 212 AN: 2284

European-Non Finnish (NFE) AF: 0.0525 AC: 23157 AN: 441212

Other (OTH) AF: 0.101 AC: 3139 AN: 31108

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

African (AFR) AF: 0.130 AC: 5336 AN: 41128

American (AMR) AF: 0.0767 AC: 1159 AN: 15102

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 357 AN: 3458

East Asian (EAS) AF: 0.227 AC: 1166 AN: 5126

South Asian (SAS) AF: 0.296 AC: 1400 AN: 4724

European-Finnish (FIN) AF: 0.107 AC: 1109 AN: 10410

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0532 AC: 3610 AN: 67850

Other (OTH) AF: 0.0982 AC: 205 AN: 2088

Alfa AF: 0.0734 Hom.: 77

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
PhyloP100		-0.14
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: rs11636419; hg19: chr15-75047600; COSMIC: COSV59659448;