Genetic Variant NAT1:c.*318T>G (chr8-18223238-T-G) – 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.*318T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.651 in 168,204 control chromosomes in the GnomAD database, including 36,695 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 ( 32583 hom., cov: 32)

Exomes 𝑓: 0.71 ( 4112 hom. )

Consequence

NAT1
NM_000662.8 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0120

Publications

17 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=-0.89).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.739 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000662.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
NAT1	NM_000662.8	MANE Select	c.*318T>G	3_prime_UTR	Exon 3 of 3	NP_000653.3
NAT1	NM_001160175.4		c.*318T>G	3_prime_UTR	Exon 5 of 5	NP_001153647.1
NAT1	NM_001160176.4		c.*318T>G	3_prime_UTR	Exon 4 of 4	NP_001153648.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
NAT1	ENST00000307719.9	TSL:1 MANE Select	c.*318T>G	3_prime_UTR	Exon 3 of 3	ENSP00000307218.4
NAT1	ENST00000518029.5	TSL:1	c.*318T>G	3_prime_UTR	Exon 4 of 4	ENSP00000428270.1
NAT1	ENST00000545197.3	TSL:5	c.*318T>G	3_prime_UTR	Exon 4 of 4	ENSP00000443194.1

Frequencies

GnomAD3 genomes

AF:

0.645

AC:

97890

AN:

151762

Hom.:

32564

Cov.:

show subpopulations

Gnomad AFR

AF:

0.492

Gnomad AMI

AF:

0.726

Gnomad AMR

AF:

0.626

Gnomad ASJ

AF:

0.722

Gnomad EAS

AF:

0.471

Gnomad SAS

AF:

0.599

Gnomad FIN

AF:

0.703

Gnomad MID

AF:

0.624

Gnomad NFE

AF:

0.744

Gnomad OTH

AF:

0.651

GnomAD4 exome

AF:

0.708

AC:

11564

AN:

16326

Hom.:

4112

Cov.:

AF XY:

0.705

AC XY:

5487

AN XY:

7780

show subpopulations

African (AFR)

AF:

0.480

AC:

AN:

American (AMR)

AF:

0.740

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.656

AC:

AN:

East Asian (EAS)

AF:

0.568

AC:

AN:

132

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AF:

0.708

AC:

10367

AN:

14640

Middle Eastern (MID)

AF:

0.333

AC:

AN:

European-Non Finnish (NFE)

AF:

0.738

AC:

884

AN:

1198

Other (OTH)

AF:

0.725

AC:

129

AN:

178

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

163

326

489

652

815

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.645

AC:

97947

AN:

151878

Hom.:

32583

Cov.:

AF XY:

0.641

AC XY:

47544

AN XY:

74222

show subpopulations

African (AFR)

AF:

0.492

AC:

20398

AN:

41420

American (AMR)

AF:

0.626

AC:

9556

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.722

AC:

2504

AN:

3470

East Asian (EAS)

AF:

0.471

AC:

2425

AN:

5148

South Asian (SAS)

AF:

0.599

AC:

2894

AN:

4828

European-Finnish (FIN)

AF:

0.703

AC:

7390

AN:

10508

Middle Eastern (MID)

AF:

0.627

AC:

183

AN:

292

European-Non Finnish (NFE)

AF:

0.744

AC:

50577

AN:

67938

Other (OTH)

AF:

0.646

AC:

1358

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1679

3358

5037

6716

8395

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

784

1568

2352

3136

3920

<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:

0.704

Hom.:

96468

Bravo

AF:

0.633

Asia WGS

AF:

0.530

AC:

1831

AN:

3456

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

4.9

(source)

DANN

Benign

0.83

PhyloP100

-0.012

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over