8-18390099-T-C

Variant names:

• chr8-18390099-T-C
• rs4646243
• XM_017012938.2:c.-7+3063T>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+3063T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 152,182 control chromosomes in the GnomAD database, including 2,368 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 0.16 (2368 hom., cov: 32)
• Consequence: NAT2 XM_017012938.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.65
• Publications: 6 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAT2	XM_017012938.2	c.-7+3063T>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: 0.159 AC: 24185 AN: 152064 Hom.: 2368 Cov.: 32

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.0844

Gnomad EAS AF: 0.487

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.202

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.146

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

GnomAD4 genome AF: 0.159 AC: 24196 AN: 152182 Hom.: 2368 Cov.: 32 AF XY: 0.164 AC XY: 12195 AN XY: 74414

African (AFR) AF: 0.110 AC: 4551 AN: 41530

American (AMR) AF: 0.225 AC: 3445 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0844 AC: 293 AN: 3472

East Asian (EAS) AF: 0.486 AC: 2505 AN: 5158

South Asian (SAS) AF: 0.141 AC: 678 AN: 4824

European-Finnish (FIN) AF: 0.202 AC: 2138 AN: 10592

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.149 AC: 10125 AN: 67986

Other (OTH) AF: 0.150 AC: 317 AN: 2114

Alfa AF: 0.141 Hom.: 239

Bravo AF: 0.163

Asia WGS AF: 0.288 AC: 1004 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.81
DANN	Benign	0.72
PhyloP100		-1.6

Splicing

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

Other links and lift over

dbSNP: rs4646243; hg19: chr8-18247609;