Variant 8-18400484-C-T 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.481C>T(p.Leu161=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.403 in 1,612,718 control chromosomes in the GnomAD database, including 136,934 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 ( 10492 hom., cov: 29)

Exomes 𝑓: 0.41 ( 126442 hom. )

Consequence

NAT2
NM_000015.3 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.00900

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=-0.5).

BP6

Variant 8-18400484-C-T is Benign according to our data. Variant chr8-18400484-C-T is described in ClinVar as [Benign]. Clinvar id is 3060382.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=0.009 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.427 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NAT2	NM_000015.3 linkuse as main transcript	c.481C>T	p.Leu161=	synonymous_variant	2/2	ENST00000286479.4
NAT2	XM_017012938.2 linkuse as main transcript	c.481C>T	p.Leu161=	synonymous_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAT2	ENST00000286479.4 linkuse as main transcript	c.481C>T	p.Leu161=	synonymous_variant	2/2	1	NM_000015.3	P1
NAT2	ENST00000520116.1 linkuse as main transcript	c.91C>T	p.Leu31=	synonymous_variant	2/2	3

Frequencies

GnomAD3 genomes

AF:

0.358

AC:

54155

AN:

151434

Hom.:

10488

Cov.:

show subpopulations

Gnomad AFR

AF:

0.260

Gnomad AMI

AF:

0.338

Gnomad AMR

AF:

0.339

Gnomad ASJ

AF:

0.435

Gnomad EAS

AF:

0.0362

Gnomad SAS

AF:

0.306

Gnomad FIN

AF:

0.443

Gnomad MID

AF:

0.434

Gnomad NFE

AF:

0.431

Gnomad OTH

AF:

0.375

GnomAD3 exomes

AF:

0.361

AC:

90469

AN:

250414

Hom.:

18050

AF XY:

0.366

AC XY:

49605

AN XY:

135422

show subpopulations

Gnomad AFR exome

AF:

0.257

Gnomad AMR exome

AF:

0.299

Gnomad ASJ exome

AF:

0.439

Gnomad EAS exome

AF:

0.0383

Gnomad SAS exome

AF:

0.310

Gnomad FIN exome

AF:

0.438

Gnomad NFE exome

AF:

0.438

Gnomad OTH exome

AF:

0.397

GnomAD4 exome

AF:

0.408

AC:

596117

AN:

1461166

Hom.:

126442

Cov.:

AF XY:

0.407

AC XY:

295485

AN XY:

726878

show subpopulations

Gnomad4 AFR exome

AF:

0.261

Gnomad4 AMR exome

AF:

0.305

Gnomad4 ASJ exome

AF:

0.433

Gnomad4 EAS exome

AF:

0.0271

Gnomad4 SAS exome

AF:

0.309

Gnomad4 FIN exome

AF:

0.434

Gnomad4 NFE exome

AF:

0.437

Gnomad4 OTH exome

AF:

0.391

GnomAD4 genome

AF:

0.358

AC:

54182

AN:

151552

Hom.:

10492

Cov.:

AF XY:

0.354

AC XY:

26219

AN XY:

73992

show subpopulations

Gnomad4 AFR

AF:

0.260

Gnomad4 AMR

AF:

0.339

Gnomad4 ASJ

AF:

0.435

Gnomad4 EAS

AF:

0.0363

Gnomad4 SAS

AF:

0.307

Gnomad4 FIN

AF:

0.443

Gnomad4 NFE

AF:

0.431

Gnomad4 OTH

AF:

0.371

Alfa

AF:

0.412

Hom.:

33505

Bravo

AF:

0.346

Asia WGS

AF:

0.178

AC:

620

AN:

3478

EpiCase

AF:

0.431

EpiControl

AF:

0.429

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

Dec 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

-0.50

CADD

Benign

5.4

DANN

Benign

0.55

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