dbSNP rs8190862: NAT1:c.*472C>G (chr8-18223392-C-G) – 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.*472C>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 0.0173 in 167,152 control chromosomes in the GnomAD database, including 50 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

Frequency

Genomes: 𝑓 0.018 ( 49 hom., cov: 32)

Exomes 𝑓: 0.0086 ( 1 hom. )

Consequence

NAT1
NM_000662.8 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.81

Publications

5 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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new If you want to explore the variant's impact on the transcript NM_000662.8, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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 sas. GnomAd4 allele frequency = 0.0182 (2764/152260) while in subpopulation SAS AF = 0.0363 (175/4822). AF 95% confidence interval is 0.0319. There are 49 homozygotes in GnomAd4. There are 1300 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.

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	UniProt
NAT1	NM_000662.8	MANE Select	c.*472C>G	3_prime_UTR	Exon 3 of 3	NP_000653.3
NAT1	NM_001160175.4		c.*472C>G	3_prime_UTR	Exon 5 of 5	NP_001153647.1	F5H5R8
NAT1	NM_001160176.4		c.*472C>G	3_prime_UTR	Exon 4 of 4	NP_001153648.1	F5H5R8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NAT1	ENST00000307719.9	TSL:1 MANE Select	c.*472C>G	3_prime_UTR	Exon 3 of 3	ENSP00000307218.4	P18440
NAT1	ENST00000518029.5	TSL:1	c.*472C>G	3_prime_UTR	Exon 4 of 4	ENSP00000428270.1	P18440
NAT1	ENST00000545197.3	TSL:5	c.*472C>G	3_prime_UTR	Exon 4 of 4	ENSP00000443194.1	F5H5R8

Frequencies

GnomAD3 genomes

AF:

0.0181

AC:

2756

AN:

152142

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:

0.0356

Gnomad FIN

AF:

0.00886

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.0255

Gnomad OTH

AF:

0.0229

GnomAD4 exome

AF:

0.00860

AC:

128

AN:

14892

Hom.:

Cov.:

AF XY:

0.0102

AC XY:

AN XY:

7080

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)

AC:

AN:

European-Finnish (FIN)

AF:

0.00824

AC:

121

AN:

14684

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0588

AC:

AN:

102

Other (OTH)

AF:

0.0111

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

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:

152260

Hom.:

Cov.:

AF XY:

0.0175

AC XY:

1300

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.00491

AC:

204

AN:

41564

American (AMR)

AF:

0.0147

AC:

225

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0421

AC:

146

AN:

3468

East Asian (EAS)

AF:

0.00656

AC:

AN:

5186

South Asian (SAS)

AF:

0.0363

AC:

175

AN:

4822

European-Finnish (FIN)

AF:

0.00886

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.0850

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0256

AC:

1738

AN:

68006

Other (OTH)

AF:

0.0232

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

137

274

412

549

686

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:

0.0263

Hom.:

Bravo

AF:

0.0174

Asia WGS

AF:

0.0240

AC:

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.78

(source)

DANN

Benign

0.63

PhyloP100

-3.8

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over