Genetic Variant NAT1:c.-87T>C (chr8-18209886-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001291962.2(NAT1):c.-87T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.756 in 152,064 control chromosomes in the GnomAD database, including 44,237 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 0.76 ( 44225 hom., cov: 30)

Exomes 𝑓: 0.93 ( 12 hom. )

Consequence

NAT1
NM_001291962.2 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.00

Publications

11 publications found

Variant links:

Genes affected

NAT1 (HGNC:7645): (N-acetyltransferase 1) This gene is one of two arylamine N-acetyltransferase (NAT) genes in the human genome, and is orthologous to the mouse and rat Nat2 genes. The enzyme encoded by this gene catalyzes the transfer of an acetyl group from acetyl-CoA to various arylamine and hydrazine substrates. This enzyme helps metabolize drugs and other xenobiotics, and functions in folate catabolism. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]

NAT1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.907 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001291962.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NAT1	NM_001291962.2		c.-87T>C	5_prime_UTR	Exon 3 of 6	NP_001278891.1	F5H5R8
NAT1	NM_001160179.3		c.-155T>C	5_prime_UTR	Exon 3 of 5	NP_001153651.1	P18440
NAT1	NM_000662.8	MANE Select	c.-380T>C	upstream_gene	N/A	NP_000653.3

Ensembl Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein
NAT1	ENST00000903000.1	c.-273T>C	5_prime_UTR	Exon 3 of 6	ENSP00000573059.1
NAT1	ENST00000903001.1	c.-273T>C	5_prime_UTR	Exon 4 of 7	ENSP00000573060.1
NAT1	ENST00000903002.1	c.-155T>C	5_prime_UTR	Exon 4 of 6	ENSP00000573061.1

Frequencies

GnomAD3 genomes

AF:

0.756

AC:

114832

AN:

151918

Hom.:

44160

Cov.:

show subpopulations

Gnomad AFR

AF:

0.914

Gnomad AMI

AF:

0.712

Gnomad AMR

AF:

0.687

Gnomad ASJ

AF:

0.731

Gnomad EAS

AF:

0.619

Gnomad SAS

AF:

0.659

Gnomad FIN

AF:

0.716

Gnomad MID

AF:

0.794

Gnomad NFE

AF:

0.701

Gnomad OTH

AF:

0.740

GnomAD4 exome

AF:

0.929

AC:

AN:

Hom.:

Cov.:

AF XY:

0.917

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.917

AC:

AN:

Other (OTH)

AF:

1.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.756

AC:

114957

AN:

152036

Hom.:

44225

Cov.:

AF XY:

0.752

AC XY:

55855

AN XY:

74302

show subpopulations

African (AFR)

AF:

0.914

AC:

37938

AN:

41494

American (AMR)

AF:

0.687

AC:

10502

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.731

AC:

2538

AN:

3472

East Asian (EAS)

AF:

0.619

AC:

3182

AN:

5144

South Asian (SAS)

AF:

0.660

AC:

3172

AN:

4808

European-Finnish (FIN)

AF:

0.716

AC:

7555

AN:

10556

Middle Eastern (MID)

AF:

0.796

AC:

234

AN:

294

European-Non Finnish (NFE)

AF:

0.701

AC:

47625

AN:

67960

Other (OTH)

AF:

0.740

AC:

1563

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1368

2735

4103

5470

6838

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

842

1684

2526

3368

4210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.725

Hom.:

100948

Bravo

AF:

0.760

Asia WGS

AF:

0.661

AC:

2299

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

1.5

(source)

DANN

Benign

0.60

PhyloP100

-2.0

PromoterAI

-0.035

Neutral

(source)

Mutation Taster

=298/2

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over