dbSNP rs8190863: NAT1:c.*504C>T (chr8-18223424-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.*504C>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 0.0173 in 167,106 control chromosomes in the GnomAD database, including 50 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: 0.0085 ( 1 hom. )

Consequence

NAT1
NM_000662.8 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.228

Publications

6 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=-0.91).

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0182 (2764/152228) while in subpopulation SAS AF = 0.0365 (176/4820). AF 95% confidence interval is 0.0321. There are 49 homozygotes in GnomAd4. There are 1298 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 2764 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAT1	NM_000662.8 link	c.*504C>T		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.*504C>T		3_prime_UTR_variant	Exon 3 of 3	1	NM_000662.8	ENSP00000307218.4		P18440

Frequencies

GnomAD3 genomes

AF:

0.0181

AC:

2756

AN:

152108

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:

0.00654

Gnomad SAS

AF:

0.0359

Gnomad FIN

AF:

0.00877

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.0255

Gnomad OTH

AF:

0.0230

GnomAD4 exome

AF:

0.00854

AC:

127

AN:

14878

Hom.:

Cov.:

AF XY:

0.0102

AC XY:

AN XY:

7070

show subpopulations

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)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.00818

AC:

120

AN:

14674

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0612

AC:

AN:

Other (OTH)

AF:

0.0111

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0182

AC:

2764

AN:

152228

Hom.:

Cov.:

AF XY:

0.0174

AC XY:

1298

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.00491

AC:

204

AN:

41560

American (AMR)

AF:

0.0147

AC:

225

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.0421

AC:

146

AN:

3468

East Asian (EAS)

AF:

0.00656

AC:

AN:

5184

South Asian (SAS)

AF:

0.0365

AC:

176

AN:

4820

European-Finnish (FIN)

AF:

0.00877

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.0850

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0256

AC:

1738

AN:

67992

Other (OTH)

AF:

0.0232

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

140

279

419

558

698

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:

0.0236

Hom.:

126

Bravo

AF:

0.0174

Asia WGS

AF:

0.0240

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.79

(source)

DANN

Benign

0.48

PhyloP100

-0.23

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