rs1208

Variant names:

• chr8-18400806-G-A
• rs1208
• NM_000015.3:c.803G>A

Your query was ambiguous. Multiple possible variants found:

• chr8-18400806-G-A
• chr8-18400806-G-C
• chr8-18400806-G-T

Variant summary

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

The ENST00000286479.4(NAT2):​c.803G>A​(p.Arg268Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.592 in 1,610,782 control chromosomes in the GnomAD database, including 286,455 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 Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.60 (28055 hom., cov: 31)
  • Exomes 𝑓: 0.59 (258400 hom.)
• Consequence: NAT2 ENST00000286479.4 missense
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.0830
• Publications: 297 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=6.8380643E-7).
• BP6: Variant 8-18400806-G-A is Benign according to our data. Variant chr8-18400806-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3059207.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.938 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000286479.4. 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.803G>A	p.Arg268Lys	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.803G>A	p.Arg268Lys	missense	Exon 2 of 2	ENSP00000286479.3	P11245
	NAT2	ENST00000893781.1		c.803G>A	p.Arg268Lys	missense	Exon 3 of 3	ENSP00000563840.1
	NAT2	ENST00000893782.1		c.803G>A	p.Arg268Lys	missense	Exon 3 of 3	ENSP00000563841.1

Frequencies

GnomAD3 genomes AF: 0.602 AC: 91371 AN: 151750 Hom.: 28047 Cov.: 31

Gnomad AFR AF: 0.601

Gnomad AMI AF: 0.677

Gnomad AMR AF: 0.635

Gnomad ASJ AF: 0.559

Gnomad EAS AF: 0.960

Gnomad SAS AF: 0.650

Gnomad FIN AF: 0.553

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.574

Gnomad OTH AF: 0.594

GnomAD2 exomes AF: 0.619 AC: 153259 AN: 247584 AF XY: 0.617

Gnomad AFR exome AF: 0.597

Gnomad AMR exome AF: 0.657

Gnomad ASJ exome AF: 0.558

Gnomad EAS exome AF: 0.959

Gnomad FIN exome AF: 0.558

Gnomad NFE exome AF: 0.567

Gnomad OTH exome AF: 0.587

GnomAD4 exome AF: 0.591 AC: 862387 AN: 1458914 Hom.: 258400 Cov.: 39 AF XY: 0.592 AC XY: 429292 AN XY: 725744

African (AFR) AF: 0.595 AC: 19826 AN: 33324

American (AMR) AF: 0.655 AC: 29011 AN: 44264

Ashkenazi Jewish (ASJ) AF: 0.565 AC: 14709 AN: 26048

East Asian (EAS) AF: 0.965 AC: 38277 AN: 39680

South Asian (SAS) AF: 0.646 AC: 55345 AN: 85722

European-Finnish (FIN) AF: 0.563 AC: 29812 AN: 52942

Middle Eastern (MID) AF: 0.543 AC: 3124 AN: 5754

European-Non Finnish (NFE) AF: 0.573 AC: 636098 AN: 1110896

Other (OTH) AF: 0.600 AC: 36185 AN: 60284

GnomAD4 genome AF: 0.602 AC: 91412 AN: 151868 Hom.: 28055 Cov.: 31 AF XY: 0.604 AC XY: 44838 AN XY: 74208

African (AFR) AF: 0.600 AC: 24861 AN: 41406

American (AMR) AF: 0.635 AC: 9688 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.559 AC: 1940 AN: 3468

East Asian (EAS) AF: 0.960 AC: 4925 AN: 5130

South Asian (SAS) AF: 0.649 AC: 3128 AN: 4818

European-Finnish (FIN) AF: 0.553 AC: 5825 AN: 10534

Middle Eastern (MID) AF: 0.531 AC: 155 AN: 292

European-Non Finnish (NFE) AF: 0.574 AC: 39012 AN: 67938

Other (OTH) AF: 0.598 AC: 1262 AN: 2112

Alfa AF: 0.583 Hom.: 92509

Bravo AF: 0.607

TwinsUK AF: 0.572 AC: 2120

ALSPAC AF: 0.581 AC: 2238

ESP6500AA AF: 0.601 AC: 2646

ESP6500EA AF: 0.576 AC: 4951

ExAC AF: 0.615 AC: 74582

Asia WGS AF: 0.779 AC: 2709 AN: 3478

EpiCase AF: 0.570

EpiControl AF: 0.572

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	NAT2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.84	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.3
DANN	Benign	0.24
DEOGEN2	Benign	0.0040	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0028	N
LIST_S2	Benign	0.035	T
MetaRNN	Benign	6.8e-7	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.083
PrimateAI	Benign	0.35	T
PROVEAN	Benign	1.4	N
REVEL	Benign	0.041
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.013
MPC		0.0046
ClinPred		0.000022	T
GERP RS		1.5
gMVP		0.47
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: rs1208; hg19: chr8-18258316; COSMIC: COSV54061405;