rs4646241

Variant names:

• chr8-18389186-T-C
• rs4646241
• XM_017012938.2:c.-7+2150T>C

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+2150T>C 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 152,106 control chromosomes in the GnomAD database, including 5,754 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 (5754 hom., cov: 32)
• Consequence: NAT2 XM_017012938.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.34
• 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=-0.9).
• 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: 41049 AN: 151988 Hom.: 5754 Cov.: 32

Gnomad AFR AF: 0.256

Gnomad AMI AF: 0.496

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.318

Gnomad EAS AF: 0.265

Gnomad SAS AF: 0.349

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.287

Gnomad OTH AF: 0.284

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

GnomAD4 genome AF: 0.270 AC: 41054 AN: 152106 Hom.: 5754 Cov.: 32 AF XY: 0.266 AC XY: 19815 AN XY: 74354

African (AFR) AF: 0.256 AC: 10609 AN: 41476

American (AMR) AF: 0.208 AC: 3176 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.318 AC: 1102 AN: 3470

East Asian (EAS) AF: 0.266 AC: 1376 AN: 5172

South Asian (SAS) AF: 0.347 AC: 1666 AN: 4806

European-Finnish (FIN) AF: 0.235 AC: 2488 AN: 10590

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

European-Non Finnish (NFE) AF: 0.287 AC: 19515 AN: 67992

Other (OTH) AF: 0.282 AC: 595 AN: 2108

Alfa AF: 0.279 Hom.: 10142

Bravo AF: 0.263

Asia WGS AF: 0.309 AC: 1074 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.5
DANN	Benign	0.68
PhyloP100		1.3

Splicing

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

Other links and lift over

dbSNP: rs4646241; hg19: chr8-18246696;