rs1799931

Variant names:

• chr8-18400860-G-A
• rs1799931
• NM_000015.3:c.857G>A

Your query was ambiguous. Multiple possible variants found:

• chr8-18400860-G-A
• chr8-18400860-G-C

Variant summary

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

The ENST00000520116.1(NAT2):​c.467G>A​(p.Gly156Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0345 in 1,592,210 control chromosomes in the GnomAD database, including 1,691 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as drug response (no stars).

• Frequency:
  • Genomes: 𝑓 0.041 (228 hom., cov: 33)
  • Exomes 𝑓: 0.034 (1463 hom.)
• Consequence: NAT2 ENST00000520116.1 missense
• Clinical Significance: drug response no assertion criteria provided O:1
• Conservation: PhyloP100: -1.92
• Publications: 378 publications found

Genes affected

NAT2 (HGNC:7646): (N-acetyltransferase 2) This gene encodes an enzyme that functions to both activate and deactivate arylamine and hydrazine drugs and carcinogens. Polymorphisms in this gene are responsible for the N-acetylation polymorphism in which human populations segregate into rapid, intermediate, and slow acetylator phenotypes. Polymorphisms in this gene are also associated with higher incidences of cancer and drug toxicity. A second polymorphic arylamine N-acetyltransferase gene (NAT1), is located near this gene (NAT2). [provided by RefSeq, Sep 2019]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0016905367).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000520116.1. 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
	NAT2	NM_000015.3	MANE Select	c.857G>A	p.Gly286Glu	missense	Exon 2 of 2	NP_000006.2	P11245

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAT2	ENST00000286479.4	TSL:1 MANE Select	c.857G>A	p.Gly286Glu	missense	Exon 2 of 2	ENSP00000286479.3	P11245
	NAT2	ENST00000893781.1		c.857G>A	p.Gly286Glu	missense	Exon 3 of 3	ENSP00000563840.1
	NAT2	ENST00000893782.1		c.857G>A	p.Gly286Glu	missense	Exon 3 of 3	ENSP00000563841.1

Frequencies

GnomAD3 genomes AF: 0.0413 AC: 6284 AN: 152096 Hom.: 227 Cov.: 33

Gnomad AFR AF: 0.0331

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0958

Gnomad ASJ AF: 0.0205

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.0739

Gnomad FIN AF: 0.0340

Gnomad MID AF: 0.0478

Gnomad NFE AF: 0.0257

Gnomad OTH AF: 0.0545

GnomAD2 exomes AF: 0.0576 AC: 13017 AN: 226094 AF XY: 0.0539

Gnomad AFR exome AF: 0.0299

Gnomad AMR exome AF: 0.142

Gnomad ASJ exome AF: 0.0190

Gnomad EAS exome AF: 0.155

Gnomad FIN exome AF: 0.0367

Gnomad NFE exome AF: 0.0250

Gnomad OTH exome AF: 0.0510

GnomAD4 exome AF: 0.0338 AC: 48617 AN: 1439998 Hom.: 1463 Cov.: 32 AF XY: 0.0341 AC XY: 24432 AN XY: 715712

African (AFR) AF: 0.0293 AC: 944 AN: 32224

American (AMR) AF: 0.137 AC: 5553 AN: 40414

Ashkenazi Jewish (ASJ) AF: 0.0179 AC: 440 AN: 24566

East Asian (EAS) AF: 0.126 AC: 5001 AN: 39600

South Asian (SAS) AF: 0.0690 AC: 5653 AN: 81894

European-Finnish (FIN) AF: 0.0370 AC: 1929 AN: 52084

Middle Eastern (MID) AF: 0.0463 AC: 260 AN: 5610

European-Non Finnish (NFE) AF: 0.0239 AC: 26411 AN: 1104226

Other (OTH) AF: 0.0409 AC: 2426 AN: 59380

GnomAD4 genome AF: 0.0414 AC: 6297 AN: 152212 Hom.: 228 Cov.: 33 AF XY: 0.0446 AC XY: 3319 AN XY: 74430

African (AFR) AF: 0.0330 AC: 1372 AN: 41542

American (AMR) AF: 0.0962 AC: 1470 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0205 AC: 71 AN: 3468

East Asian (EAS) AF: 0.151 AC: 779 AN: 5164

South Asian (SAS) AF: 0.0740 AC: 356 AN: 4814

European-Finnish (FIN) AF: 0.0340 AC: 360 AN: 10602

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0257 AC: 1751 AN: 68018

Other (OTH) AF: 0.0573 AC: 121 AN: 2112

Alfa AF: 0.0326 Hom.: 601

Bravo AF: 0.0470

TwinsUK AF: 0.0227 AC: 84

ALSPAC AF: 0.0197 AC: 76

ESP6500AA AF: 0.0288 AC: 126

ESP6500EA AF: 0.0199 AC: 170

ExAC AF: 0.0520 AC: 6297

Asia WGS AF: 0.106 AC: 367 AN: 3478

ClinVar

ClinVar submissions

Significance: drug response

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	-	Slow acetylator due to N-acetyltransferase enzyme variant (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.0020
DANN	Benign	0.29
DEOGEN2	Benign	0.0074	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0083	N
LIST_S2	Benign	0.036	T
MetaRNN	Benign	0.0017	T
MetaSVM	Benign	-0.93	T
PhyloP100		-1.9
PrimateAI	Benign	0.23	T
PROVEAN	Benign	1.4	N
REVEL	Benign	0.022
Sift	Benign	0.48	T
Sift4G	Benign	0.97	T
Polyphen		0.32	B
Vest4		0.11
MPC		0.0041
ClinPred		0.0054	T
GERP RS		-5.1
gMVP		0.65
Mutation Taster		=97/3	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: rs1799931; hg19: chr8-18258370; COSMIC: COSV99673956;