rs8192784

Variant names:

• chr19-41088545-G-A
• rs8192784
• NM_000766.5:c.74G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-41088545-G-A
• chr19-41088545-G-C
• chr19-41088545-G-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.74G>A​(p.Arg25Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0228 in 1,613,868 control chromosomes in the GnomAD database, including 1,551 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 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 (641 hom., cov: 31)
  • Exomes 𝑓: 0.019 (910 hom.)
• Consequence: CYP2A13 NM_000766.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.728
• Publications: 18 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=0.0013855398).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.167 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2A13	NM_000766.5	c.74G>A	p.Arg25Gln	missense_variant	Exon 1 of 9	ENST00000330436.4	NP_000757.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP2A13	ENST00000330436.4	c.74G>A	p.Arg25Gln	missense_variant	Exon 1 of 9	1	NM_000766.5	ENSP00000332679.1

Frequencies

GnomAD3 genomes AF: 0.0607 AC: 9227 AN: 152064 Hom.: 638 Cov.: 31

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0336

Gnomad ASJ AF: 0.0542

Gnomad EAS AF: 0.0735

Gnomad SAS AF: 0.0328

Gnomad FIN AF: 0.00509

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0112

Gnomad OTH AF: 0.0517

GnomAD2 exomes AF: 0.0306 AC: 7688 AN: 251276 AF XY: 0.0284

Gnomad AFR exome AF: 0.166

Gnomad AMR exome AF: 0.0155

Gnomad ASJ exome AF: 0.0575

Gnomad EAS exome AF: 0.0717

Gnomad FIN exome AF: 0.00517

Gnomad NFE exome AF: 0.0116

Gnomad OTH exome AF: 0.0249

GnomAD4 exome AF: 0.0188 AC: 27543 AN: 1461686 Hom.: 910 Cov.: 32 AF XY: 0.0188 AC XY: 13659 AN XY: 727162

African (AFR) AF: 0.177 AC: 5929 AN: 33472

American (AMR) AF: 0.0170 AC: 758 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.0568 AC: 1483 AN: 26132

East Asian (EAS) AF: 0.0712 AC: 2827 AN: 39700

South Asian (SAS) AF: 0.0291 AC: 2509 AN: 86246

European-Finnish (FIN) AF: 0.00565 AC: 302 AN: 53418

Middle Eastern (MID) AF: 0.0352 AC: 203 AN: 5764

European-Non Finnish (NFE) AF: 0.0104 AC: 11585 AN: 1111860

Other (OTH) AF: 0.0322 AC: 1947 AN: 60380

GnomAD4 genome AF: 0.0608 AC: 9251 AN: 152182 Hom.: 641 Cov.: 31 AF XY: 0.0598 AC XY: 4446 AN XY: 74408

African (AFR) AF: 0.171 AC: 7077 AN: 41478

American (AMR) AF: 0.0335 AC: 513 AN: 15298

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

East Asian (EAS) AF: 0.0739 AC: 383 AN: 5184

South Asian (SAS) AF: 0.0330 AC: 159 AN: 4820

European-Finnish (FIN) AF: 0.00509 AC: 54 AN: 10610

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

European-Non Finnish (NFE) AF: 0.0112 AC: 759 AN: 68006

Other (OTH) AF: 0.0512 AC: 108 AN: 2110

Alfa AF: 0.0282 Hom.: 68

Bravo AF: 0.0668

TwinsUK AF: 0.00917 AC: 34

ALSPAC AF: 0.0106 AC: 41

ESP6500AA AF: 0.147 AC: 648

ESP6500EA AF: 0.0140 AC: 120

ExAC AF: 0.0335 AC: 4062

EpiCase AF: 0.0142

EpiControl AF: 0.0131

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.70	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	2.6
DANN	Benign	0.89
DEOGEN2	Benign	0.052	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.10	T
MetaRNN	Benign	0.0014	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.23	N
PhyloP100		-0.73
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.98	N
REVEL	Benign	0.063
Sift	Benign	0.22	T
Sift4G	Benign	0.15	T
Vest4		0.029
ClinPred		0.0015	T
GERP RS		1.1
PromoterAI		-0.027	Neutral
Varity_R		0.041
gMVP		0.28
Mutation Taster		=99/1	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: rs8192784; hg19: chr19-41594450; COSMIC: COSV57839158;