dbSNP rs4986989: NAT1:c.-6-34A>T (chr8-18222008-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_001160174.3(NAT1):c.-40A>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0214 in 1,565,808 control chromosomes in the GnomAD database, including 454 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 0.018 ( 49 hom., cov: 32)

Exomes 𝑓: 0.022 ( 405 hom. )

Consequence

NAT1
NM_001160174.3 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.102

Publications

18 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=-0.96).

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.074 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001160174.3. 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_000662.8	MANE Select	c.-6-34A>T	intron	N/A	NP_000653.3
NAT1	NM_001160174.3		c.-40A>T	5_prime_UTR	Exon 1 of 1	NP_001153646.1	P18440
NAT1	NM_001160175.4		c.181-34A>T	intron	N/A	NP_001153647.1	F5H5R8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NAT1	ENST00000307719.9	TSL:1 MANE Select	c.-6-34A>T	intron	N/A	ENSP00000307218.4	P18440
NAT1	ENST00000518029.5	TSL:1	c.-6-34A>T	intron	N/A	ENSP00000428270.1	P18440
NAT1	ENST00000519006.5	TSL:1	n.522-34A>T	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0181

AC:

2751

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00487

Gnomad AMI

AF:

0.0811

Gnomad AMR

AF:

0.0147

Gnomad ASJ

AF:

0.0421

Gnomad EAS

AF:

0.00653

Gnomad SAS

AF:

0.0358

Gnomad FIN

AF:

0.00877

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.0255

Gnomad OTH

AF:

0.0225

GnomAD2 exomes

AF:

0.0204

AC:

4363

AN:

214154

AF XY:

0.0217

show subpopulations

Gnomad AFR exome

AF:

0.00381

Gnomad AMR exome

AF:

0.0116

Gnomad ASJ exome

AF:

0.0449

Gnomad EAS exome

AF:

0.00787

Gnomad FIN exome

AF:

0.00869

Gnomad NFE exome

AF:

0.0257

Gnomad OTH exome

AF:

0.0294

GnomAD4 exome

AF:

0.0218

AC:

30751

AN:

1413478

Hom.:

405

Cov.:

AF XY:

0.0223

AC XY:

15555

AN XY:

698222

show subpopulations

African (AFR)

AF:

0.00510

AC:

162

AN:

31746

American (AMR)

AF:

0.0118

AC:

440

AN:

37386

Ashkenazi Jewish (ASJ)

AF:

0.0453

AC:

1042

AN:

22998

East Asian (EAS)

AF:

0.00588

AC:

231

AN:

39276

South Asian (SAS)

AF:

0.0273

AC:

2109

AN:

77262

European-Finnish (FIN)

AF:

0.00951

AC:

492

AN:

51722

Middle Eastern (MID)

AF:

0.0802

AC:

435

AN:

5426

European-Non Finnish (NFE)

AF:

0.0223

AC:

24253

AN:

1089334

Other (OTH)

AF:

0.0272

AC:

1587

AN:

58328

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

1513

3025

4538

6050

7563

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

848

1696

2544

3392

4240

<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:

0.0181

AC:

2759

AN:

152330

Hom.:

Cov.:

AF XY:

0.0174

AC XY:

1297

AN XY:

74482

show subpopulations

African (AFR)

AF:

0.00491

AC:

204

AN:

41570

American (AMR)

AF:

0.0147

AC:

225

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0421

AC:

146

AN:

3472

East Asian (EAS)

AF:

0.00654

AC:

AN:

5196

South Asian (SAS)

AF:

0.0365

AC:

176

AN:

4826

European-Finnish (FIN)

AF:

0.00877

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.0850

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0255

AC:

1734

AN:

68032

Other (OTH)

AF:

0.0227

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

135

269

404

538

673

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

144

180

<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:

0.0269

Hom.:

Bravo

AF:

0.0174

Asia WGS

AF:

0.0240

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

3.4

(source)

DANN

Benign

0.80

PhyloP100

0.10

PromoterAI

0.0022

Neutral

(source)

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