8-18393412-T-C

Position:

• chr8-18393412-T-C

Variant summary

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

The ENST00000286479.4(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 ENST00000286479.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.814

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.444 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NAT2	NM_000015.3	c.-7+2067T>C		intron_variant		ENST00000286479.4	NP_000006.2
NAT2	XM_017012938.2	c.-7+6376T>C		intron_variant			XP_016868427.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NAT2	ENST00000286479.4	c.-7+2067T>C		intron_variant		1	NM_000015.3	ENSP00000286479	P1
NAT2	ENST00000520116.1	c.-58+2067T>C		intron_variant		3		ENSP00000428416

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

Gnomad4 AFR AF: 0.304

Gnomad4 AMR AF: 0.359

Gnomad4 ASJ AF: 0.448

Gnomad4 EAS AF: 0.0411

Gnomad4 SAS AF: 0.353

Gnomad4 FIN AF: 0.469

Gnomad4 NFE AF: 0.448

Gnomad4 OTH AF: 0.388

Alfa AF: 0.435 Hom.: 14223

Bravo AF: 0.371

Asia WGS AF: 0.211 AC: 734 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.9
DANN	Benign	0.73

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: rs9987109; hg19: chr8-18250922;