NM_000015.3:c.-7+2067T>C

Variant names:

• chr8-18393412-T-C
• rs9987109
• NM_000015.3:c.-7+2067T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000015.3(NAT2):​c.-7+2067T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.383 in 152,000 control chromosomes in the GnomAD database, including 11,867 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 0.38 (11867 hom., cov: 31)
• Consequence: NAT2 NM_000015.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.814
• Publications: 8 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.444 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000015.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAT2	NM_000015.3	MANE Select	c.-7+2067T>C		intron	N/A	NP_000006.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAT2	ENST00000286479.4	TSL:1 MANE Select	c.-7+2067T>C		intron	N/A	ENSP00000286479.3
	NAT2	ENST00000520116.1	TSL:3	c.-58+2067T>C		intron	N/A	ENSP00000428416.1

Frequencies

GnomAD3 genomes AF: 0.383 AC: 58153 AN: 151882 Hom.: 11857 Cov.: 31

Gnomad AFR AF: 0.304

Gnomad AMI AF: 0.348

Gnomad AMR AF: 0.359

Gnomad ASJ AF: 0.448

Gnomad EAS AF: 0.0411

Gnomad SAS AF: 0.352

Gnomad FIN AF: 0.469

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.448

Gnomad OTH AF: 0.392

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

GnomAD4 genome AF: 0.383 AC: 58192 AN: 152000 Hom.: 11867 Cov.: 31 AF XY: 0.380 AC XY: 28217 AN XY: 74296

African (AFR) AF: 0.304 AC: 12586 AN: 41450

American (AMR) AF: 0.359 AC: 5477 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.448 AC: 1557 AN: 3472

East Asian (EAS) AF: 0.0411 AC: 212 AN: 5152

South Asian (SAS) AF: 0.353 AC: 1700 AN: 4820

European-Finnish (FIN) AF: 0.469 AC: 4959 AN: 10564

Middle Eastern (MID) AF: 0.449 AC: 131 AN: 292

European-Non Finnish (NFE) AF: 0.448 AC: 30434 AN: 67962

Other (OTH) AF: 0.388 AC: 819 AN: 2112

Alfa AF: 0.430 Hom.: 18289

Bravo AF: 0.371

Asia WGS AF: 0.211 AC: 734 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.9
DANN	Benign	0.73
PhyloP100		-0.81
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9987109; hg19: chr8-18250922;