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.

Variant Effect in Transcripts

 

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

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 v4.9

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;