rs2470890

Variant names:

• chr15-74755085-T-C
• rs2470890
• NM_000761.5:c.1548T>C

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_000761.5(CYP1A2):​c.1548T>C​(p.Asn516Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.429 in 1,602,572 control chromosomes in the GnomAD database, including 173,535 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.57 (29243 hom., cov: 32)
  • Exomes 𝑓: 0.41 (144292 hom.)
• Consequence: CYP1A2 NM_000761.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.219
• Publications: 155 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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 15-74755085-T-C is Benign according to our data. Variant chr15-74755085-T-C is described in ClinVar as Benign. ClinVar VariationId is 768718.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.219 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.878 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP1A2	NM_000761.5	MANE Select	c.1548T>C	p.Asn516Asn	synonymous	Exon 7 of 7	NP_000752.2	P05177

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP1A2	ENST00000343932.5	TSL:1 MANE Select	c.1548T>C	p.Asn516Asn	synonymous	Exon 7 of 7	ENSP00000342007.4	P05177
	CYP1A2	ENST00000872480.1		c.1563T>C	p.Asn521Asn	synonymous	Exon 7 of 7	ENSP00000542539.1
	CYP1A2	ENST00000872476.1		c.1548T>C	p.Asn516Asn	synonymous	Exon 7 of 7	ENSP00000542535.1

Frequencies

GnomAD3 genomes AF: 0.572 AC: 86870 AN: 151998 Hom.: 29170 Cov.: 32

Gnomad AFR AF: 0.885

Gnomad AMI AF: 0.544

Gnomad AMR AF: 0.650

Gnomad ASJ AF: 0.451

Gnomad EAS AF: 0.843

Gnomad SAS AF: 0.807

Gnomad FIN AF: 0.441

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.353

Gnomad OTH AF: 0.552

GnomAD4 exome AF: 0.414 AC: 600555 AN: 1450458 Hom.: 144292 Cov.: 47 AF XY: 0.423 AC XY: 304798 AN XY: 719852

African (AFR) AF: 0.904 AC: 30129 AN: 33344

American (AMR) AF: 0.728 AC: 32480 AN: 44624

Ashkenazi Jewish (ASJ) AF: 0.447 AC: 11653 AN: 26080

East Asian (EAS) AF: 0.814 AC: 32161 AN: 39510

South Asian (SAS) AF: 0.791 AC: 68116 AN: 86152

European-Finnish (FIN) AF: 0.434 AC: 21692 AN: 49934

Middle Eastern (MID) AF: 0.497 AC: 2757 AN: 5546

European-Non Finnish (NFE) AF: 0.338 AC: 373912 AN: 1105318

Other (OTH) AF: 0.461 AC: 27655 AN: 59950

GnomAD4 genome AF: 0.572 AC: 87007 AN: 152114 Hom.: 29243 Cov.: 32 AF XY: 0.585 AC XY: 43463 AN XY: 74342

African (AFR) AF: 0.886 AC: 36779 AN: 41522

American (AMR) AF: 0.650 AC: 9940 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.451 AC: 1563 AN: 3466

East Asian (EAS) AF: 0.843 AC: 4353 AN: 5162

South Asian (SAS) AF: 0.808 AC: 3901 AN: 4828

European-Finnish (FIN) AF: 0.441 AC: 4652 AN: 10548

Middle Eastern (MID) AF: 0.463 AC: 136 AN: 294

European-Non Finnish (NFE) AF: 0.353 AC: 24013 AN: 67988

Other (OTH) AF: 0.557 AC: 1176 AN: 2112

Alfa AF: 0.431 Hom.: 50971

Bravo AF: 0.593

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	1.7
PhyloP100		0.22

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2470890; hg19: chr15-75047426;