chr8-18398199-A-G

Position:

• chr8-18398199-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000015.3(NAT2):​c.-6-1799A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.334 in 152,018 control chromosomes in the GnomAD database, including 9,044 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 0.33 (9044 hom., cov: 32)
• Consequence: NAT2 NM_000015.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.347

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.65 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NAT2	NM_000015.3	c.-6-1799A>G		intron_variant		ENST00000286479.4	NP_000006.2
NAT2	XM_017012938.2	c.-6-1799A>G		intron_variant			XP_016868427.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NAT2	ENST00000286479.4	c.-6-1799A>G		intron_variant		1	NM_000015.3	ENSP00000286479.3
NAT2	ENST00000520116.1	c.-57-2138A>G		intron_variant		3		ENSP00000428416.1

Frequencies

GnomAD3 genomes AF: 0.334 AC: 50738 AN: 151902 Hom.: 9032 Cov.: 32

Gnomad AFR AF: 0.339

Gnomad AMI AF: 0.343

Gnomad AMR AF: 0.435

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.669

Gnomad SAS AF: 0.303

Gnomad FIN AF: 0.324

Gnomad MID AF: 0.268

Gnomad NFE AF: 0.293

Gnomad OTH AF: 0.322

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

GnomAD4 genome AF: 0.334 AC: 50785 AN: 152018 Hom.: 9044 Cov.: 32 AF XY: 0.339 AC XY: 25213 AN XY: 74288

Gnomad4 AFR AF: 0.338

Gnomad4 AMR AF: 0.436

Gnomad4 ASJ AF: 0.224

Gnomad4 EAS AF: 0.668

Gnomad4 SAS AF: 0.305

Gnomad4 FIN AF: 0.324

Gnomad4 NFE AF: 0.293

Gnomad4 OTH AF: 0.327

Alfa AF: 0.304 Hom.: 7158

Bravo AF: 0.348

Asia WGS AF: 0.448 AC: 1558 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	9.1
DANN	Benign	0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1961456; hg19: chr8-18255709;