Variant rs1041983 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_000015.3(NAT2):c.282C>T(p.Tyr94=) variant causes a synonymous 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
NM_000015.3 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.0750

Variant links:

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]

NAT2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 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.

BP7

Synonymous conserved (PhyloP=-0.075 with no splicing effect.

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/exons	MANE	Protein	UniProt
NAT2	NM_000015.3 linkuse as main transcript	c.282C>T	p.Tyr94=	synonymous_variant	2/2	ENST00000286479.4	NP_000006.2
NAT2	XM_017012938.2 linkuse as main transcript	c.282C>T	p.Tyr94=	synonymous_variant	3/3		XP_016868427.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NAT2	ENST00000286479.4 linkuse as main transcript	c.282C>T	p.Tyr94=	synonymous_variant	2/2	1	NM_000015.3	ENSP00000286479	P1
NAT2	ENST00000520116.1 linkuse as main transcript	c.-57-52C>T		intron_variant		3		ENSP00000428416

Frequencies

GnomAD3 genomes

AF:

0.360

AC:

54604

AN:

151710

Hom.:

10194

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.331

AC XY:

240168

AN XY:

726604

show subpopulations

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.:

AF XY:

0.359

AC XY:

26637

AN XY:

74218

show subpopulations

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

LINK: link

Submissions by phenotype

NAT2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 29, 2023

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over