Genetic Variant NAT1:c.*215A>T (chr8-18223135-A-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_000662.8(NAT1):c.*215A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.673 in 149,482 control chromosomes in the GnomAD database, including 34,413 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 0.67 ( 34413 hom., cov: 31)

Exomes 𝑓: 0.69 ( 11308 hom. )

Failed GnomAD Quality Control

Consequence

NAT1
NM_000662.8 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00

Publications

40 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:

Genome browser will be placed here

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=-0.99).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.77 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAT1	NM_000662.8 link	c.*215A>T		3_prime_UTR_variant	Exon 3 of 3	ENST00000307719.9	NP_000653.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAT1	ENST00000307719.9 link	c.*215A>T		3_prime_UTR_variant	Exon 3 of 3	1	NM_000662.8	ENSP00000307218.4

Frequencies

GnomAD3 genomes

AF:

0.673

AC:

100474

AN:

149370

Hom.:

34395

Cov.:

show subpopulations

Gnomad AFR

AF:

0.522

Gnomad AMI

AF:

0.759

Gnomad AMR

AF:

0.641

Gnomad ASJ

AF:

0.741

Gnomad EAS

AF:

0.486

Gnomad SAS

AF:

0.625

Gnomad FIN

AF:

0.733

Gnomad MID

AF:

0.662

Gnomad NFE

AF:

0.776

Gnomad OTH

AF:

0.676

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.693

AC:

34417

AN:

49684

Hom.:

11308

Cov.:

AF XY:

0.696

AC XY:

17632

AN XY:

25322

show subpopulations

African (AFR)

AF:

0.501

AC:

622

AN:

1242

American (AMR)

AF:

0.609

AC:

700

AN:

1150

Ashkenazi Jewish (ASJ)

AF:

0.721

AC:

1022

AN:

1418

East Asian (EAS)

AF:

0.492

AC:

1465

AN:

2976

South Asian (SAS)

AF:

0.569

AC:

215

AN:

378

European-Finnish (FIN)

AF:

0.674

AC:

9887

AN:

14676

Middle Eastern (MID)

AF:

0.683

AC:

112

AN:

164

European-Non Finnish (NFE)

AF:

0.742

AC:

18727

AN:

25254

Other (OTH)

AF:

0.687

AC:

1667

AN:

2426

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.529

Heterozygous variant carriers

429

857

1286

1714

2143

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

200

300

400

500

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.673

AC:

100528

AN:

149482

Hom.:

34413

Cov.:

AF XY:

0.667

AC XY:

48760

AN XY:

73092

show subpopulations

African (AFR)

AF:

0.522

AC:

21371

AN:

40964

American (AMR)

AF:

0.641

AC:

9646

AN:

15052

Ashkenazi Jewish (ASJ)

AF:

0.741

AC:

2502

AN:

3378

East Asian (EAS)

AF:

0.486

AC:

2484

AN:

5106

South Asian (SAS)

AF:

0.626

AC:

2945

AN:

4708

European-Finnish (FIN)

AF:

0.733

AC:

7490

AN:

10212

Middle Eastern (MID)

AF:

0.668

AC:

183

AN:

274

European-Non Finnish (NFE)

AF:

0.776

AC:

51863

AN:

66852

Other (OTH)

AF:

0.670

AC:

1390

AN:

2074

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1633

3266

4899

6532

8165

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

788

1576

2364

3152

3940

<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:

0.702

Hom.:

3626

Bravo

AF:

0.658

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

1.4

(source)

DANN

Benign

0.34

PhyloP100

0.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over