19-41089049-C-T

Variant names:

• chr19-41089049-C-T
• rs72552266
• NM_000766.5:c.301C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 1P and 4B. PP3 BS2

The NM_000766.5(CYP2A13):​c.301C>T​(p.Arg101*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00715 in 1,611,914 control chromosomes in the GnomAD database, including 59 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. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.0058 (4 hom., cov: 31)
  • Exomes 𝑓: 0.0073 (55 hom.)
• Consequence: CYP2A13 NM_000766.5 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0300
• Publications: 21 publications found

Genes affected

CYP2A13 (HGNC:2608): (cytochrome P450 family 2 subfamily A member 13) 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. This protein localizes to the endoplasmic reticulum. Although its endogenous substrate has not been determined, it is known to metabolize 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, a major nitrosamine specific to tobacco. This gene is part of a large cluster of cytochrome P450 genes from the CYP2A, CYP2B and CYP2F subfamilies on chromosome 19q. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000766.5. 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
	CYP2A13	NM_000766.5	MANE Select	c.301C>T	p.Arg101*	stop_gained	Exon 2 of 9	NP_000757.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2A13	ENST00000330436.4	TSL:1 MANE Select	c.301C>T	p.Arg101*	stop_gained	Exon 2 of 9	ENSP00000332679.1

Frequencies

GnomAD3 genomes AF: 0.00585 AC: 888 AN: 151880 Hom.: 4 Cov.: 31

Gnomad AFR AF: 0.00165

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.00675

Gnomad ASJ AF: 0.000867

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.00187

Gnomad FIN AF: 0.00170

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00958

Gnomad OTH AF: 0.00718

GnomAD2 exomes AF: 0.00575 AC: 1441 AN: 250608 AF XY: 0.00575

Gnomad AFR exome AF: 0.00111

Gnomad AMR exome AF: 0.00553

Gnomad ASJ exome AF: 0.00119

Gnomad EAS exome AF: 0.00174

Gnomad FIN exome AF: 0.00125

Gnomad NFE exome AF: 0.00938

Gnomad OTH exome AF: 0.00621

GnomAD4 exome AF: 0.00729 AC: 10645 AN: 1459918 Hom.: 55 Cov.: 32 AF XY: 0.00727 AC XY: 5277 AN XY: 726158

African (AFR) AF: 0.00129 AC: 43 AN: 33410

American (AMR) AF: 0.00616 AC: 275 AN: 44678

Ashkenazi Jewish (ASJ) AF: 0.00135 AC: 35 AN: 26016

East Asian (EAS) AF: 0.00312 AC: 124 AN: 39700

South Asian (SAS) AF: 0.00232 AC: 200 AN: 86060

European-Finnish (FIN) AF: 0.00210 AC: 112 AN: 53370

Middle Eastern (MID) AF: 0.00805 AC: 41 AN: 5092

European-Non Finnish (NFE) AF: 0.00852 AC: 9464 AN: 1111340

Other (OTH) AF: 0.00583 AC: 351 AN: 60252

GnomAD4 genome AF: 0.00584 AC: 887 AN: 151996 Hom.: 4 Cov.: 31 AF XY: 0.00557 AC XY: 414 AN XY: 74302

African (AFR) AF: 0.00164 AC: 68 AN: 41414

American (AMR) AF: 0.00675 AC: 103 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.000867 AC: 3 AN: 3460

East Asian (EAS) AF: 0.00213 AC: 11 AN: 5172

South Asian (SAS) AF: 0.00187 AC: 9 AN: 4808

European-Finnish (FIN) AF: 0.00170 AC: 18 AN: 10610

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.00958 AC: 651 AN: 67944

Other (OTH) AF: 0.00710 AC: 15 AN: 2112

Alfa AF: 0.00720 Hom.: 1

Bravo AF: 0.00589

ExAC AF: 0.00593 AC: 720

EpiCase AF: 0.00922

EpiControl AF: 0.0104

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.033	T
BayesDel_noAF	Pathogenic	0.19
CADD	Pathogenic	38
DANN	Uncertain	0.99
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.46
FATHMM_MKL	Benign	0.24	N
PhyloP100		0.030
Vest4		0.55
GERP RS		2.4
Mutation Taster		=152/48	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.63		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.63		Position offset: -2

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

Other links and lift over

dbSNP: rs72552266; hg19: chr19-41594954; COSMIC: COSV57839004;