rs1801279

Variant names:

• chr8-18400194-G-A
• rs1801279
• NM_000015.3:c.191G>A

Your query was ambiguous. Multiple possible variants found:

• chr8-18400194-G-A
• chr8-18400194-G-C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_000015.3(NAT2):​c.191G>A​(p.Arg64Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00455 in 1,613,190 control chromosomes in the GnomAD database, including 273 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign,drug response (no stars).

• Frequency:
  • Genomes: 𝑓 0.024 (148 hom., cov: 32)
  • Exomes 𝑓: 0.0025 (125 hom.)
• Consequence: NAT2 NM_000015.3 missense
• Clinical Significance: Likely benign; drug response no assertion criteria provided B:1 O:1
• Conservation: PhyloP100: 4.28
• Publications: 198 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0065536797).
• BP6: Variant 8-18400194-G-A is Benign according to our data. Variant chr8-18400194-G-A is described in ClinVar as Likely_benign|drug_response. ClinVar VariationId is 726.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0803 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000015.3. 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.191G>A	p.Arg64Gln	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.191G>A	p.Arg64Gln	missense	Exon 2 of 2	ENSP00000286479.3	P11245
	NAT2	ENST00000893781.1		c.191G>A	p.Arg64Gln	missense	Exon 3 of 3	ENSP00000563840.1
	NAT2	ENST00000893782.1		c.191G>A	p.Arg64Gln	missense	Exon 3 of 3	ENSP00000563841.1

Frequencies

GnomAD3 genomes AF: 0.0241 AC: 3658 AN: 152072 Hom.: 147 Cov.: 32

Gnomad AFR AF: 0.0826

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0114

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000397

Gnomad OTH AF: 0.0182

GnomAD2 exomes AF: 0.00620 AC: 1554 AN: 250678 AF XY: 0.00447

Gnomad AFR exome AF: 0.0822

Gnomad AMR exome AF: 0.00452

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000464

Gnomad NFE exome AF: 0.000309

Gnomad OTH exome AF: 0.00344

GnomAD4 exome AF: 0.00251 AC: 3673 AN: 1461002 Hom.: 125 Cov.: 30 AF XY: 0.00211 AC XY: 1535 AN XY: 726678

African (AFR) AF: 0.0856 AC: 2861 AN: 33438

American (AMR) AF: 0.00515 AC: 230 AN: 44672

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26088

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39688

South Asian (SAS) AF: 0.000197 AC: 17 AN: 86194

European-Finnish (FIN) AF: 0.0000375 AC: 2 AN: 53398

Middle Eastern (MID) AF: 0.00417 AC: 24 AN: 5760

European-Non Finnish (NFE) AF: 0.000182 AC: 202 AN: 1111416

Other (OTH) AF: 0.00557 AC: 336 AN: 60348

GnomAD4 genome AF: 0.0241 AC: 3669 AN: 152188 Hom.: 148 Cov.: 32 AF XY: 0.0237 AC XY: 1766 AN XY: 74406

African (AFR) AF: 0.0826 AC: 3428 AN: 41492

American (AMR) AF: 0.0114 AC: 174 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.000397 AC: 27 AN: 68000

Other (OTH) AF: 0.0180 AC: 38 AN: 2112

Alfa AF: 0.0128 Hom.: 138

Bravo AF: 0.0273

ESP6500AA AF: 0.0772 AC: 340

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.00787 AC: 955

Asia WGS AF: 0.00549 AC: 20 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000652

ClinVar

ClinVar submissions

Significance: Likely benign; drug response

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	NAT2-related disorder (1)
-	-	-	Slow acetylator due to N-acetyltransferase enzyme variant (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.61
CADD	Uncertain	23
DANN	Uncertain	1.0
Eigen	Benign	0.059
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.84	T
MetaRNN	Benign	0.0066	T
MetaSVM	Benign	-1.2	T
PhyloP100		4.3
PrimateAI	Benign	0.33	T
PROVEAN	Uncertain	-3.9	D
REVEL	Benign	0.23
Sift	Uncertain	0.0090	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.28
MVP		0.29
MPC		0.019
ClinPred		0.066	T
GERP RS		1.1
gMVP		0.84
Mutation Taster		=90/10	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1801279; hg19: chr8-18257704;