XM_017012938.2:c.-7+3667A>T

Variant names:

• chr8-18390703-A-T
• rs4345601
• XM_017012938.2:c.-7+3667A>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+3667A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 146,436 control chromosomes in the GnomAD database, including 1,056 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 (1056 hom., cov: 32)
• Consequence: NAT2 XM_017012938.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.564
• Publications: 3 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.183 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: 0.111 AC: 16179 AN: 146328 Hom.: 1052 Cov.: 32

Gnomad AFR AF: 0.0447

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.188

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.159

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.135

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

GnomAD4 genome AF: 0.111 AC: 16194 AN: 146436 Hom.: 1056 Cov.: 32 AF XY: 0.114 AC XY: 8154 AN XY: 71408

African (AFR) AF: 0.0446 AC: 1796 AN: 40308

American (AMR) AF: 0.189 AC: 2738 AN: 14516

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 503 AN: 3354

East Asian (EAS) AF: 0.180 AC: 925 AN: 5136

South Asian (SAS) AF: 0.165 AC: 751 AN: 4562

European-Finnish (FIN) AF: 0.107 AC: 1028 AN: 9652

Middle Eastern (MID) AF: 0.170 AC: 48 AN: 282

European-Non Finnish (NFE) AF: 0.123 AC: 8080 AN: 65740

Other (OTH) AF: 0.137 AC: 272 AN: 1990

Alfa AF: 0.112 Hom.: 125

Bravo AF: 0.110

Asia WGS AF: 0.154 AC: 532 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.1
DANN	Benign	0.69
PhyloP100		-0.56

Splicing

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

Other links and lift over

dbSNP: rs4345601; hg19: chr8-18248213;