rs4345600

Variant names:

• chr8-18390698-A-G
• rs4345600
• XM_017012938.2:c.-7+3662A>G

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+3662A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 149,752 control chromosomes in the GnomAD database, including 1,052 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 0.11 (1052 hom., cov: 32)
• Consequence: NAT2 XM_017012938.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.366
• Publications: 11 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.178 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: 0.108 AC: 16175 AN: 149644 Hom.: 1048 Cov.: 32

Gnomad AFR AF: 0.0439

Gnomad AMI AF: 0.0586

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.146

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.159

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.129

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

GnomAD4 genome AF: 0.108 AC: 16190 AN: 149752 Hom.: 1052 Cov.: 32 AF XY: 0.111 AC XY: 8145 AN XY: 73088

African (AFR) AF: 0.0438 AC: 1796 AN: 40980

American (AMR) AF: 0.183 AC: 2738 AN: 14924

Ashkenazi Jewish (ASJ) AF: 0.146 AC: 503 AN: 3438

East Asian (EAS) AF: 0.180 AC: 927 AN: 5140

South Asian (SAS) AF: 0.160 AC: 750 AN: 4702

European-Finnish (FIN) AF: 0.102 AC: 1028 AN: 10092

Middle Eastern (MID) AF: 0.167 AC: 48 AN: 288

European-Non Finnish (NFE) AF: 0.120 AC: 8075 AN: 67214

Other (OTH) AF: 0.131 AC: 272 AN: 2070

Alfa AF: 0.120 Hom.: 1179

Bravo AF: 0.110

Asia WGS AF: 0.153 AC: 531 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.1
DANN	Benign	0.89
PhyloP100		-0.37

Splicing

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

Other links and lift over

dbSNP: rs4345600; hg19: chr8-18248208;