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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAT2	XM_017012938.2	c.-7+2150T>C		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: 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 v4.3

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;