rs2470890

Positions:

• chr15-74755085-T-C

Variant summary

Our verdict is Benign. Variant got -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

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 -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP1A2	NM_000761.5	c.1548T>C	p.Asn516Asn	synonymous_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.1548T>C	p.Asn516Asn	synonymous_variant	7/7	1	NM_000761.5	ENSP00000342007.4

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

Gnomad4 AFR exome AF: 0.904

Gnomad4 AMR exome AF: 0.728

Gnomad4 ASJ exome AF: 0.447

Gnomad4 EAS exome AF: 0.814

Gnomad4 SAS exome AF: 0.791

Gnomad4 FIN exome AF: 0.434

Gnomad4 NFE exome AF: 0.338

Gnomad4 OTH exome AF: 0.461

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

Gnomad4 AFR AF: 0.886

Gnomad4 AMR AF: 0.650

Gnomad4 ASJ AF: 0.451

Gnomad4 EAS AF: 0.843

Gnomad4 SAS AF: 0.808

Gnomad4 FIN AF: 0.441

Gnomad4 NFE AF: 0.353

Gnomad4 OTH AF: 0.557

Alfa AF: 0.406 Hom.: 17505

Bravo AF: 0.593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2470890; hg19: chr15-75047426;