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.

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: 0.159 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 v4.9

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;