rs4646244

Variant names:

• chr8-18390208-T-A
• rs4646244
• XM_017012938.2:c.-7+3172T>A

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+3172T>A 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 151,968 control chromosomes in the GnomAD database, including 5,744 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 (5744 hom., cov: 33)
• Consequence: NAT2 XM_017012938.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.221
• Publications: 17 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.333 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAT2	XM_017012938.2	c.-7+3172T>A		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: 41020 AN: 151848 Hom.: 5744 Cov.: 33

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: 0.349

Gnomad FIN AF: 0.237

Gnomad MID AF: 0.264

Gnomad NFE AF: 0.287

Gnomad OTH AF: 0.283

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

GnomAD4 genome AF: 0.270 AC: 41023 AN: 151968 Hom.: 5744 Cov.: 33 AF XY: 0.267 AC XY: 19801 AN XY: 74272

African (AFR) AF: 0.256 AC: 10623 AN: 41446

American (AMR) AF: 0.208 AC: 3169 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.315 AC: 1093 AN: 3468

East Asian (EAS) AF: 0.265 AC: 1368 AN: 5168

South Asian (SAS) AF: 0.346 AC: 1665 AN: 4806

European-Finnish (FIN) AF: 0.237 AC: 2494 AN: 10524

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

European-Non Finnish (NFE) AF: 0.287 AC: 19491 AN: 67974

Other (OTH) AF: 0.281 AC: 595 AN: 2114

Alfa AF: 0.275 Hom.: 743

Bravo AF: 0.262

Asia WGS AF: 0.308 AC: 1071 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.9
DANN	Benign	0.64
PhyloP100		0.22

Splicing

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

Other links and lift over

dbSNP: rs4646244; hg19: chr8-18247718;