NM_000766.5:c.769C>T

Variant names:

• chr19-41091846-C-T
• rs8192789
• NM_000766.5:c.769C>T

Variant summary

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

The NM_000766.5(CYP2A13):​c.769C>T​(p.Arg257Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0231 in 1,614,062 control chromosomes in the GnomAD database, including 1,508 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.061 (639 hom., cov: 31)
  • Exomes 𝑓: 0.019 (869 hom.)
• Consequence: CYP2A13 NM_000766.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.398
• Publications: 41 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0015957355).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.169 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2A13	NM_000766.5	c.769C>T	p.Arg257Cys	missense_variant	Exon 5 of 9	ENST00000330436.4	NP_000757.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP2A13	ENST00000330436.4	c.769C>T	p.Arg257Cys	missense_variant	Exon 5 of 9	1	NM_000766.5	ENSP00000332679.1

Frequencies

GnomAD3 genomes AF: 0.0613 AC: 9332 AN: 152114 Hom.: 636 Cov.: 31

Gnomad AFR AF: 0.172

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0338

Gnomad ASJ AF: 0.0542

Gnomad EAS AF: 0.0734

Gnomad SAS AF: 0.0325

Gnomad FIN AF: 0.00762

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0113

Gnomad OTH AF: 0.0517

GnomAD2 exomes AF: 0.0312 AC: 7854 AN: 251488 AF XY: 0.0290

Gnomad AFR exome AF: 0.170

Gnomad AMR exome AF: 0.0155

Gnomad ASJ exome AF: 0.0574

Gnomad EAS exome AF: 0.0720

Gnomad FIN exome AF: 0.00790

Gnomad NFE exome AF: 0.0117

Gnomad OTH exome AF: 0.0254

GnomAD4 exome AF: 0.0191 AC: 27856 AN: 1461830 Hom.: 869 Cov.: 31 AF XY: 0.0190 AC XY: 13805 AN XY: 727222

African (AFR) AF: 0.179 AC: 5995 AN: 33448

American (AMR) AF: 0.0169 AC: 758 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0565 AC: 1476 AN: 26130

East Asian (EAS) AF: 0.0716 AC: 2841 AN: 39700

South Asian (SAS) AF: 0.0294 AC: 2540 AN: 86258

European-Finnish (FIN) AF: 0.00775 AC: 414 AN: 53420

Middle Eastern (MID) AF: 0.0361 AC: 208 AN: 5762

European-Non Finnish (NFE) AF: 0.0105 AC: 11661 AN: 1112000

Other (OTH) AF: 0.0325 AC: 1963 AN: 60390

GnomAD4 genome AF: 0.0615 AC: 9358 AN: 152232 Hom.: 639 Cov.: 31 AF XY: 0.0605 AC XY: 4504 AN XY: 74428

African (AFR) AF: 0.172 AC: 7143 AN: 41490

American (AMR) AF: 0.0337 AC: 516 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0542 AC: 188 AN: 3470

East Asian (EAS) AF: 0.0737 AC: 382 AN: 5182

South Asian (SAS) AF: 0.0327 AC: 158 AN: 4828

European-Finnish (FIN) AF: 0.00762 AC: 81 AN: 10624

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0113 AC: 772 AN: 68030

Other (OTH) AF: 0.0511 AC: 108 AN: 2112

Alfa AF: 0.0242 Hom.: 331

Bravo AF: 0.0675

TwinsUK AF: 0.00917 AC: 34

ALSPAC AF: 0.0106 AC: 41

ESP6500AA AF: 0.159 AC: 699

ESP6500EA AF: 0.0138 AC: 119

ExAC AF: 0.0341 AC: 4146

Asia WGS AF: 0.0560 AC: 195 AN: 3478

EpiCase AF: 0.0143

EpiControl AF: 0.0132

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.21	T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.092	N
LIST_S2	Benign	0.42	T
MetaRNN	Benign	0.0016	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		-0.40
PrimateAI	Benign	0.33	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.093
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.016	D
Polyphen		0.068	B
Vest4		0.081
MPC		0.14
ClinPred		0.026	T
GERP RS		0.62
Varity_R		0.44
gMVP		0.41
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: rs8192789; hg19: chr19-41597751; COSMIC: COSV57837193;