rs7011792

Variant names:

• chr8-18394559-G-C
• rs7011792
• NM_000015.3:c.-7+3214G>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+3214G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.34 in 151,910 control chromosomes in the GnomAD database, including 9,499 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 0.34 (9499 hom., cov: 31)
• Consequence: NAT2 NM_000015.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.219
• Publications: 5 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 (NFE) allele frequency at 95% confidence interval = 0.403 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAT2	NM_000015.3	c.-7+3214G>C		intron_variant	Intron 1 of 1	ENST00000286479.4	NP_000006.2
NAT2	XM_017012938.2	c.-6-5439G>C		intron_variant	Intron 2 of 2		XP_016868427.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAT2	ENST00000286479.4	c.-7+3214G>C		intron_variant	Intron 1 of 1	1	NM_000015.3	ENSP00000286479.3
NAT2	ENST00000520116.1	c.-58+3214G>C		intron_variant	Intron 1 of 1	3		ENSP00000428416.1

Frequencies

GnomAD3 genomes AF: 0.340 AC: 51620 AN: 151792 Hom.: 9492 Cov.: 31

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.286

Gnomad AMR AF: 0.335

Gnomad ASJ AF: 0.427

Gnomad EAS AF: 0.0399

Gnomad SAS AF: 0.313

Gnomad FIN AF: 0.421

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.407

Gnomad OTH AF: 0.360

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

GnomAD4 genome AF: 0.340 AC: 51656 AN: 151910 Hom.: 9499 Cov.: 31 AF XY: 0.338 AC XY: 25092 AN XY: 74220

African (AFR) AF: 0.244 AC: 10116 AN: 41432

American (AMR) AF: 0.335 AC: 5118 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.427 AC: 1481 AN: 3472

East Asian (EAS) AF: 0.0400 AC: 207 AN: 5170

South Asian (SAS) AF: 0.314 AC: 1508 AN: 4808

European-Finnish (FIN) AF: 0.421 AC: 4427 AN: 10522

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.407 AC: 27661 AN: 67942

Other (OTH) AF: 0.356 AC: 750 AN: 2104

Alfa AF: 0.380 Hom.: 1439

Bravo AF: 0.330

Asia WGS AF: 0.190 AC: 661 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.2
DANN	Benign	0.30
PhyloP100		0.22
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: rs7011792; hg19: chr8-18252069;