dbSNP rs15561: NAT1:c.*222A>C (chr8-18223142-A-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_000662.8(NAT1):c.*222A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.644 in 151,056 control chromosomes in the GnomAD database, including 32,271 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 0.64 ( 32271 hom., cov: 31)

Exomes 𝑓: 0.71 ( 11891 hom. )

Failed GnomAD Quality Control

Consequence

NAT1
NM_000662.8 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.15

Publications

53 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=-0.92).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.738 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAT1	NM_000662.8 link	c.*222A>C		3_prime_UTR_variant	Exon 3 of 3	ENST00000307719.9	NP_000653.3	P18440

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAT1	ENST00000307719.9 link	c.*222A>C		3_prime_UTR_variant	Exon 3 of 3	1	NM_000662.8	ENSP00000307218.4		P18440

Frequencies

GnomAD3 genomes

AF:

0.644

AC:

97181

AN:

150942

Hom.:

32252

Cov.:

show subpopulations

Gnomad AFR

AF:

0.491

Gnomad AMI

AF:

0.724

Gnomad AMR

AF:

0.624

Gnomad ASJ

AF:

0.721

Gnomad EAS

AF:

0.471

Gnomad SAS

AF:

0.599

Gnomad FIN

AF:

0.701

Gnomad MID

AF:

0.619

Gnomad NFE

AF:

0.744

Gnomad OTH

AF:

0.651

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.707

AC:

33425

AN:

47294

Hom.:

11891

Cov.:

AF XY:

0.709

AC XY:

17065

AN XY:

24064

show subpopulations

African (AFR)

AF:

0.499

AC:

559

AN:

1120

American (AMR)

AF:

0.636

AC:

641

AN:

1008

Ashkenazi Jewish (ASJ)

AF:

0.701

AC:

992

AN:

1416

East Asian (EAS)

AF:

0.502

AC:

1319

AN:

2626

South Asian (SAS)

AF:

0.563

AC:

198

AN:

352

European-Finnish (FIN)

AF:

0.707

AC:

10696

AN:

15124

Middle Eastern (MID)

AF:

0.659

AC:

116

AN:

176

European-Non Finnish (NFE)

AF:

0.747

AC:

17339

AN:

23204

Other (OTH)

AF:

0.690

AC:

1565

AN:

2268

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

436

872

1308

1744

2180

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

192

288

384

480

<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:

0.644

AC:

97238

AN:

151056

Hom.:

32271

Cov.:

AF XY:

0.639

AC XY:

47191

AN XY:

73800

show subpopulations

African (AFR)

AF:

0.491

AC:

20220

AN:

41200

American (AMR)

AF:

0.624

AC:

9492

AN:

15204

Ashkenazi Jewish (ASJ)

AF:

0.721

AC:

2499

AN:

3464

East Asian (EAS)

AF:

0.471

AC:

2423

AN:

5146

South Asian (SAS)

AF:

0.599

AC:

2882

AN:

4810

European-Finnish (FIN)

AF:

0.701

AC:

7197

AN:

10268

Middle Eastern (MID)

AF:

0.621

AC:

180

AN:

290

European-Non Finnish (NFE)

AF:

0.744

AC:

50331

AN:

67666

Other (OTH)

AF:

0.646

AC:

1358

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1650

3300

4949

6599

8249

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

776

1552

2328

3104

3880

<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:

0.707

Hom.:

103201

Bravo

AF:

0.633

Asia WGS

AF:

0.529

AC:

1813

AN:

3426

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.42

(source)

DANN

Benign

0.64

PhyloP100

-1.1

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

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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