Genetic Variant NM_000662.8:c.-6-338C>T (chr8-18221704-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.-6-338C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0191 in 209,604 control chromosomes in the GnomAD database, including 63 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 ( 14 hom. )

Consequence

NAT1
NM_000662.8 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.681

Publications

15 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=-1.0).

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0181 (2760/152158) while in subpopulation SAS AF = 0.0361 (174/4820). AF 95% confidence interval is 0.0317. There are 49 homozygotes in GnomAd4. There are 1295 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 2760 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.-6-338C>T	intron	N/A	NP_000653.3
NAT1	NM_001160174.3		c.-344C>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 1	NP_001153646.1	P18440
NAT1	NM_001160174.3		c.-344C>T	5_prime_UTR	Exon 1 of 1	NP_001153646.1	P18440

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NAT1	ENST00000307719.9	TSL:1 MANE Select	c.-6-338C>T	intron	N/A	ENSP00000307218.4	P18440
NAT1	ENST00000518029.5	TSL:1	c.-6-338C>T	intron	N/A	ENSP00000428270.1	P18440
NAT1	ENST00000519006.5	TSL:1	n.522-338C>T	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0181

AC:

2752

AN:

152040

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00488

Gnomad AMI

AF:

0.0802

Gnomad AMR

AF:

0.0147

Gnomad ASJ

AF:

0.0421

Gnomad EAS

AF:

0.00638

Gnomad SAS

AF:

0.0354

Gnomad FIN

AF:

0.00877

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.0255

Gnomad OTH

AF:

0.0229

GnomAD4 exome

AF:

0.0217

AC:

1244

AN:

57446

Hom.:

AF XY:

0.0229

AC XY:

687

AN XY:

30052

show subpopulations

African (AFR)

AF:

0.00467

AC:

AN:

1070

American (AMR)

AF:

0.0154

AC:

AN:

3452

Ashkenazi Jewish (ASJ)

AF:

0.0411

AC:

AN:

1510

East Asian (EAS)

AF:

0.00715

AC:

AN:

2796

South Asian (SAS)

AF:

0.0247

AC:

153

AN:

6186

European-Finnish (FIN)

AF:

0.0105

AC:

AN:

2468

Middle Eastern (MID)

AF:

0.0686

AC:

AN:

204

European-Non Finnish (NFE)

AF:

0.0229

AC:

840

AN:

36652

Other (OTH)

AF:

0.0228

AC:

AN:

3108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

112

167

223

279

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:

0.0181

AC:

2760

AN:

152158

Hom.:

Cov.:

AF XY:

0.0174

AC XY:

1295

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.00491

AC:

204

AN:

41508

American (AMR)

AF:

0.0147

AC:

225

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.0421

AC:

146

AN:

3470

East Asian (EAS)

AF:

0.00639

AC:

AN:

5162

South Asian (SAS)

AF:

0.0361

AC:

174

AN:

4820

European-Finnish (FIN)

AF:

0.00877

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.0850

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0256

AC:

1738

AN:

67996

Other (OTH)

AF:

0.0232

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

140

280

420

560

700

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:

0.0237

Hom.:

149

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

-1.0

CADD

Benign

2.0

(source)

DANN

Benign

0.52

PhyloP100

-0.68

PromoterAI

0.0081

Neutral

(source)

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over