rs762551

Variant names:

• chr15-74749576-C-A
• rs762551
• NM_000761.5:c.-9-154C>A

Your query was ambiguous. Multiple possible variants found:

• chr15-74749576-C-A
• chr15-74749576-C-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000761.5(CYP1A2):​c.-9-154C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.672 in 152,062 control chromosomes in the GnomAD database, including 34,665 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency: Genomes: 𝑓 0.67 (34665 hom., cov: 32)
• Consequence: CYP1A2 NM_000761.5 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.24
• Publications: 551 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 15-74749576-C-A is Benign according to our data. Variant chr15-74749576-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 511079.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.706 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.-9-154C>A		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.-9-154C>A		intron	N/A	ENSP00000342007.4
	CYP1A2	ENST00000872478.1		c.-163C>A		5_prime_UTR	Exon 2 of 7	ENSP00000542537.1
	CYP1A2	ENST00000872480.1		c.-9-154C>A		intron	N/A	ENSP00000542539.1

Frequencies

GnomAD3 genomes AF: 0.672 AC: 102144 AN: 151944 Hom.: 34631 Cov.: 32

Gnomad AFR AF: 0.605

Gnomad AMI AF: 0.650

Gnomad AMR AF: 0.706

Gnomad ASJ AF: 0.686

Gnomad EAS AF: 0.651

Gnomad SAS AF: 0.567

Gnomad FIN AF: 0.689

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.712

Gnomad OTH AF: 0.666

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.672 AC: 102235 AN: 152062 Hom.: 34665 Cov.: 32 AF XY: 0.668 AC XY: 49693 AN XY: 74348

African (AFR) AF: 0.605 AC: 25080 AN: 41436

American (AMR) AF: 0.706 AC: 10794 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.686 AC: 2379 AN: 3470

East Asian (EAS) AF: 0.651 AC: 3367 AN: 5170

South Asian (SAS) AF: 0.568 AC: 2738 AN: 4822

European-Finnish (FIN) AF: 0.689 AC: 7305 AN: 10600

Middle Eastern (MID) AF: 0.684 AC: 201 AN: 294

European-Non Finnish (NFE) AF: 0.712 AC: 48375 AN: 67968

Other (OTH) AF: 0.667 AC: 1406 AN: 2108

Alfa AF: 0.695 Hom.: 73795

Bravo AF: 0.676

Asia WGS AF: 0.661 AC: 2300 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.0070
DANN	Benign	0.69
PhyloP100		-1.2
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: rs762551; hg19: chr15-75041917; COSMIC: COSV59659144;