rs1041983

Variant names:

• chr8-18400285-C-T
• rs1041983
• NM_000015.3:c.282C>T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The ENST00000520116.1(NAT2):​c.-57-52C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 1,612,606 control chromosomes in the GnomAD database, including 90,622 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.36 (10196 hom., cov: 31)
  • Exomes 𝑓: 0.33 (80426 hom.)
• Consequence: NAT2 ENST00000520116.1 intron
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.0750

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 8-18400285-C-T is Benign according to our data. Variant chr8-18400285-C-T is described in ClinVar as [Benign]. Clinvar id is 3060182.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.444 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAT2	NM_000015.3	c.282C>T	p.Tyr94Tyr	synonymous_variant	Exon 2 of 2	ENST00000286479.4	NP_000006.2
NAT2	XM_017012938.2	c.282C>T	p.Tyr94Tyr	synonymous_variant	Exon 3 of 3		XP_016868427.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAT2	ENST00000286479.4	c.282C>T	p.Tyr94Tyr	synonymous_variant	Exon 2 of 2	1	NM_000015.3	ENSP00000286479.3
NAT2	ENST00000520116.1	c.-57-52C>T		intron_variant	Intron 1 of 1	3		ENSP00000428416.1

Frequencies

GnomAD3 genomes AF: 0.360 AC: 54604 AN: 151710 Hom.: 10194 Cov.: 31

Gnomad AFR AF: 0.450

Gnomad AMI AF: 0.355

Gnomad AMR AF: 0.321

Gnomad ASJ AF: 0.382

Gnomad EAS AF: 0.412

Gnomad SAS AF: 0.439

Gnomad FIN AF: 0.267

Gnomad MID AF: 0.334

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.362

GnomAD3 exomes AF: 0.342 AC: 85599 AN: 250306 Hom.: 15264 AF XY: 0.344 AC XY: 46546 AN XY: 135260

Gnomad AFR exome AF: 0.449

Gnomad AMR exome AF: 0.304

Gnomad ASJ exome AF: 0.372

Gnomad EAS exome AF: 0.419

Gnomad SAS exome AF: 0.428

Gnomad FIN exome AF: 0.274

Gnomad NFE exome AF: 0.313

Gnomad OTH exome AF: 0.330

GnomAD4 exome AF: 0.328 AC: 479746 AN: 1460778 Hom.: 80426 Cov.: 39 AF XY: 0.331 AC XY: 240168 AN XY: 726604

Gnomad4 AFR exome AF: 0.455

Gnomad4 AMR exome AF: 0.307

Gnomad4 ASJ exome AF: 0.382

Gnomad4 EAS exome AF: 0.352

Gnomad4 SAS exome AF: 0.428

Gnomad4 FIN exome AF: 0.278

Gnomad4 NFE exome AF: 0.317

Gnomad4 OTH exome AF: 0.347

GnomAD4 genome AF: 0.360 AC: 54628 AN: 151828 Hom.: 10196 Cov.: 31 AF XY: 0.359 AC XY: 26637 AN XY: 74218

Gnomad4 AFR AF: 0.449

Gnomad4 AMR AF: 0.321

Gnomad4 ASJ AF: 0.382

Gnomad4 EAS AF: 0.413

Gnomad4 SAS AF: 0.437

Gnomad4 FIN AF: 0.267

Gnomad4 NFE AF: 0.318

Gnomad4 OTH AF: 0.363

Alfa AF: 0.327 Hom.: 17518

Bravo AF: 0.363

Asia WGS AF: 0.432 AC: 1503 AN: 3478

EpiCase AF: 0.319

EpiControl AF: 0.318

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

NAT2-related disorder Benign:1

Mar 29, 2023

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.48
DANN	Benign	0.28

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: rs1041983; hg19: chr8-18257795; COSMIC: COSV54061508;