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8-18400484-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

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 (★).

Frequency

Genomes: 𝑓 0.36 ( 10492 hom., cov: 29)
Exomes 𝑓: 0.41 ( 126442 hom. )

Consequence

NAT2
NM_000015.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter 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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.5).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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 criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.009 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
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
NAT2NM_000015.3 linkuse as main transcriptc.481C>T p.Leu161= synonymous_variant 2/2 ENST00000286479.4
NAT2XM_017012938.2 linkuse as main transcriptc.481C>T p.Leu161= synonymous_variant 3/3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NAT2ENST00000286479.4 linkuse as main transcriptc.481C>T p.Leu161= synonymous_variant 2/21 NM_000015.3 P1
NAT2ENST00000520116.1 linkuse as main transcriptc.91C>T p.Leu31= synonymous_variant 2/23

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.358
AC:
54155
AN:
151434
Hom.:
10488
Cov.:
29
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.:
60
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.358
AC:
54182
AN:
151552
Hom.:
10492
Cov.:
29
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: criteria provided, single submitter
LINK: link

Submissions by phenotype

NAT2-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesDec 29, 2023This 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.

Other links and lift over

dbSNP: rs1799929; hg19: chr8-18257994; COSMIC: COSV54061442; API