rs2606345

Variant names:

• chr15-74724835-C-A
• rs2606345
• NM_001319217.2:c.-30+606G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001319217.2(CYP1A1):​c.-30+606G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.457 in 151,748 control chromosomes in the GnomAD database, including 20,353 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 0.46 (20353 hom., cov: 29)
• Consequence: CYP1A1 NM_001319217.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.134
• Publications: 74 publications found

Genes affected

CYP1A1 (HGNC:2595): (cytochrome P450 family 1 subfamily A member 1) This gene, CYP1A1, 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. This protein 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. The gene has been associated with lung cancer risk. A related family member, CYP1A2, is located approximately 25 kb away from CYP1A1 on chromosome 15. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jan 2016]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.668 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP1A1	NM_001319217.2	c.-30+606G>T		intron_variant	Intron 1 of 6	ENST00000379727.8	NP_001306146.1
CYP1A1	NM_000499.5	c.-27+606G>T		intron_variant	Intron 1 of 6		NP_000490.1
CYP1A1	NM_001319216.2	c.-30+606G>T		intron_variant	Intron 1 of 5		NP_001306145.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP1A1	ENST00000379727.8	c.-30+606G>T		intron_variant	Intron 1 of 6	1	NM_001319217.2	ENSP00000369050.3

Frequencies

GnomAD3 genomes AF: 0.457 AC: 69294 AN: 151630 Hom.: 20359 Cov.: 29

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.600

Gnomad AMR AF: 0.410

Gnomad ASJ AF: 0.545

Gnomad EAS AF: 0.0535

Gnomad SAS AF: 0.360

Gnomad FIN AF: 0.589

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.673

Gnomad OTH AF: 0.472

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

GnomAD4 genome AF: 0.457 AC: 69278 AN: 151748 Hom.: 20353 Cov.: 29 AF XY: 0.448 AC XY: 33220 AN XY: 74132

African (AFR) AF: 0.134 AC: 5558 AN: 41346

American (AMR) AF: 0.410 AC: 6244 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.545 AC: 1891 AN: 3470

East Asian (EAS) AF: 0.0536 AC: 278 AN: 5182

South Asian (SAS) AF: 0.358 AC: 1720 AN: 4804

European-Finnish (FIN) AF: 0.589 AC: 6186 AN: 10508

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.674 AC: 45722 AN: 67884

Other (OTH) AF: 0.469 AC: 989 AN: 2110

Alfa AF: 0.593 Hom.: 84874

Bravo AF: 0.430

Asia WGS AF: 0.184 AC: 643 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	11
DANN	Benign	0.79
PhyloP100		0.13
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: rs2606345; hg19: chr15-75017176;