8-18390758-G-C

Variant names:

• chr8-18390758-G-C
• rs4271002
• XM_017012938.2:c.-7+3722G>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+3722G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 152,064 control chromosomes in the GnomAD database, including 1,152 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 0.12 (1152 hom., cov: 32)
• Consequence: NAT2 XM_017012938.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17
• Publications: 25 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Variant Effect in Transcripts

 

RefSeq Transcripts

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

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17791 AN: 151944 Hom.: 1148 Cov.: 32

Gnomad AFR AF: 0.0799

Gnomad AMI AF: 0.0581

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.0977

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.135

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

GnomAD4 genome AF: 0.117 AC: 17811 AN: 152064 Hom.: 1152 Cov.: 32 AF XY: 0.121 AC XY: 8956 AN XY: 74316

African (AFR) AF: 0.0798 AC: 3311 AN: 41496

American (AMR) AF: 0.183 AC: 2795 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 501 AN: 3462

East Asian (EAS) AF: 0.180 AC: 926 AN: 5144

South Asian (SAS) AF: 0.157 AC: 754 AN: 4816

European-Finnish (FIN) AF: 0.0977 AC: 1032 AN: 10562

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.119 AC: 8101 AN: 67986

Other (OTH) AF: 0.137 AC: 289 AN: 2110

Alfa AF: 0.119 Hom.: 175

Bravo AF: 0.122

Asia WGS AF: 0.156 AC: 540 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.24
DANN	Benign	0.45
PhyloP100		-1.2

Splicing

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

Other links and lift over

dbSNP: rs4271002; hg19: chr8-18248268;