rs4646267

Variant names:

• chr8-18390403-A-G
• rs4646267
• XM_017012938.2:c.-7+3367A>G

Your query was ambiguous. Multiple possible variants found:

• chr8-18390403-A-G
• chr8-18390403-A-T

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+3367A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 152,174 control chromosomes in the GnomAD database, including 2,691 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 0.17 (2691 hom., cov: 32)
• Consequence: NAT2 XM_017012938.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.499
• 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=-0.58).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.469 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: 0.170 AC: 25789 AN: 152058 Hom.: 2691 Cov.: 32

Gnomad AFR AF: 0.0969

Gnomad AMI AF: 0.161

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.0937

Gnomad EAS AF: 0.486

Gnomad SAS AF: 0.147

Gnomad FIN AF: 0.225

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.151

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

GnomAD4 genome AF: 0.170 AC: 25798 AN: 152174 Hom.: 2691 Cov.: 32 AF XY: 0.174 AC XY: 12936 AN XY: 74396

African (AFR) AF: 0.0968 AC: 4019 AN: 41532

American (AMR) AF: 0.231 AC: 3534 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0937 AC: 325 AN: 3468

East Asian (EAS) AF: 0.485 AC: 2503 AN: 5160

South Asian (SAS) AF: 0.147 AC: 709 AN: 4816

European-Finnish (FIN) AF: 0.225 AC: 2379 AN: 10588

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.174 AC: 11823 AN: 68004

Other (OTH) AF: 0.156 AC: 328 AN: 2108

Alfa AF: 0.172 Hom.: 7778

Bravo AF: 0.171

Asia WGS AF: 0.288 AC: 1005 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	7.7
DANN	Benign	0.95
PhyloP100		0.50

Splicing

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

Other links and lift over

dbSNP: rs4646267; hg19: chr8-18247913;