rs4646242

Variant names:

• chr8-18389939-A-G
• rs4646242
• XM_017012938.2:c.-7+2903A>G

Variant summary

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

The XM_017012938.2(NAT2):​c.-7+2903A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 152,138 control chromosomes in the GnomAD database, including 5,736 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.27 (5736 hom., cov: 32)
• Consequence: NAT2 XM_017012938.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.110
• Publications: 8 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 (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.331 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAT2	XM_017012938.2	c.-7+2903A>G		intron_variant	Intron 2 of 2		XP_016868427.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.270 AC: 41011 AN: 152020 Hom.: 5736 Cov.: 32

Gnomad AFR AF: 0.256

Gnomad AMI AF: 0.496

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.315

Gnomad EAS AF: 0.264

Gnomad SAS AF: 0.347

Gnomad FIN AF: 0.236

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.287

Gnomad OTH AF: 0.282

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.270 AC: 41013 AN: 152138 Hom.: 5736 Cov.: 32 AF XY: 0.266 AC XY: 19795 AN XY: 74380

African (AFR) AF: 0.256 AC: 10611 AN: 41490

American (AMR) AF: 0.207 AC: 3175 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.315 AC: 1092 AN: 3468

East Asian (EAS) AF: 0.265 AC: 1369 AN: 5174

South Asian (SAS) AF: 0.345 AC: 1665 AN: 4822

European-Finnish (FIN) AF: 0.236 AC: 2496 AN: 10590

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.287 AC: 19487 AN: 67980

Other (OTH) AF: 0.281 AC: 592 AN: 2108

Alfa AF: 0.274 Hom.: 7634

Bravo AF: 0.262

Asia WGS AF: 0.308 AC: 1072 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.3
DANN	Benign	0.54
PhyloP100		-0.11

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4646242; hg19: chr8-18247449;