dbSNP rs8190864: NAT1:c.*581C>T (chr8-18223501-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_000662.8(NAT1):c.*581C>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 0.00551 in 150,806 control chromosomes in the GnomAD database, including 8 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 0.0055 ( 8 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

NAT1
NM_000662.8 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.692

Publications

1 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=-0.95).

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00551 (831/150806) while in subpopulation AFR AF = 0.0185 (761/41106). AF 95% confidence interval is 0.0174. There are 8 homozygotes in GnomAd4. There are 385 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 831 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAT1	NM_000662.8 link	c.*581C>T		3_prime_UTR_variant	Exon 3 of 3	ENST00000307719.9	NP_000653.3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
NAT1	ENST00000307719.9 link	c.*581C>T	3_prime_UTR_variant	Exon 3 of 3	1	NM_000662.8	ENSP00000307218.4
NAT1	ENST00000518029.5 link	c.*581C>T	3_prime_UTR_variant	Exon 4 of 4	1		ENSP00000428270.1
NAT1	ENST00000545197.3 link	c.*581C>T	3_prime_UTR_variant	Exon 4 of 4	5		ENSP00000443194.1
NAT1	ENST00000517492.5 link	c.*581C>T	3_prime_UTR_variant	Exon 3 of 3	2		ENSP00000429407.1

Frequencies

GnomAD3 genomes

AF:

0.00549

AC:

828

AN:

150688

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0185

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00258

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000209

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000266

Gnomad OTH

AF:

0.00530

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

14884

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

7070

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

14694

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

GnomAD4 genome

AF:

0.00551

AC:

831

AN:

150806

Hom.:

Cov.:

AF XY:

0.00523

AC XY:

385

AN XY:

73668

show subpopulations

African (AFR)

AF:

0.0185

AC:

761

AN:

41106

American (AMR)

AF:

0.00257

AC:

AN:

15154

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3460

East Asian (EAS)

AF:

0.00

AC:

AN:

5136

South Asian (SAS)

AF:

0.000210

AC:

AN:

4772

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10242

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000266

AC:

AN:

67636

Other (OTH)

AF:

0.00524

AC:

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

127

170

212

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.00309

Hom.:

Bravo

AF:

0.00628

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.67

(source)

DANN

Benign

0.72

PhyloP100

-0.69

Mutation Taster

=100/0

polymorphism

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over