rs7832071

Positions:

• chr8-18399770-C-T

Variant summary

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

The ENST00000286479.4(NAT2):​c.-6-228C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.395 in 151,402 control chromosomes in the GnomAD database, including 12,338 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 0.39 (12338 hom., cov: 32)
• Consequence: NAT2 ENST00000286479.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.88

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=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NAT2	NM_000015.3	c.-6-228C>T		intron_variant		ENST00000286479.4	NP_000006.2
NAT2	XM_017012938.2	c.-6-228C>T		intron_variant			XP_016868427.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NAT2	ENST00000286479.4	c.-6-228C>T		intron_variant		1	NM_000015.3	ENSP00000286479	P1
NAT2	ENST00000520116.1	c.-57-567C>T		intron_variant		3		ENSP00000428416

Frequencies

GnomAD3 genomes AF: 0.395 AC: 59713 AN: 151284 Hom.: 12326 Cov.: 32

Gnomad AFR AF: 0.403

Gnomad AMI AF: 0.325

Gnomad AMR AF: 0.355

Gnomad ASJ AF: 0.438

Gnomad EAS AF: 0.0360

Gnomad SAS AF: 0.316

Gnomad FIN AF: 0.447

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.421

Gnomad OTH AF: 0.404

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

GnomAD4 genome AF: 0.395 AC: 59759 AN: 151402 Hom.: 12338 Cov.: 32 AF XY: 0.391 AC XY: 28894 AN XY: 73988

Gnomad4 AFR AF: 0.403

Gnomad4 AMR AF: 0.355

Gnomad4 ASJ AF: 0.438

Gnomad4 EAS AF: 0.0361

Gnomad4 SAS AF: 0.317

Gnomad4 FIN AF: 0.447

Gnomad4 NFE AF: 0.421

Gnomad4 OTH AF: 0.401

Alfa AF: 0.415 Hom.: 18082

Bravo AF: 0.387

Asia WGS AF: 0.194 AC: 676 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.20
DANN	Benign	0.69

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: rs7832071; hg19: chr8-18257280;