rs1112005

Positions:

• chr8-18398366-C-T

Variant summary

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

The NM_000015.3(NAT2):​c.-6-1632C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 152,018 control chromosomes in the GnomAD database, including 4,890 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 0.25 (4890 hom., cov: 32)
• Consequence: NAT2 NM_000015.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.659

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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.329 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NAT2	NM_000015.3	c.-6-1632C>T		intron_variant		ENST00000286479.4
NAT2	XM_017012938.2	c.-6-1632C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAT2	ENST00000286479.4	c.-6-1632C>T		intron_variant		1	NM_000015.3	P1
NAT2	ENST00000520116.1	c.-57-1971C>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37760 AN: 151900 Hom.: 4896 Cov.: 32

Gnomad AFR AF: 0.204

Gnomad AMI AF: 0.346

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.334

Gnomad EAS AF: 0.256

Gnomad SAS AF: 0.345

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.279

Gnomad OTH AF: 0.257

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

GnomAD4 genome AF: 0.248 AC: 37746 AN: 152018 Hom.: 4890 Cov.: 32 AF XY: 0.246 AC XY: 18276 AN XY: 74334

Gnomad4 AFR AF: 0.204

Gnomad4 AMR AF: 0.192

Gnomad4 ASJ AF: 0.334

Gnomad4 EAS AF: 0.256

Gnomad4 SAS AF: 0.342

Gnomad4 FIN AF: 0.223

Gnomad4 NFE AF: 0.278

Gnomad4 OTH AF: 0.255

Alfa AF: 0.268 Hom.: 6926

Bravo AF: 0.239

Asia WGS AF: 0.302 AC: 1049 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.1
DANN	Benign	0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs1112005; hg19: chr8-18255876;