dbSNP rs2410545: NAT1:n.42T>C (chr8-18211326-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000519006.5(NAT1):n.42T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.726 in 152,182 control chromosomes in the GnomAD database, including 40,829 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 0.73 ( 40816 hom., cov: 31)

Exomes 𝑓: 0.65 ( 13 hom. )

Consequence

NAT1
ENST00000519006.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.92

Publications

9 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=-0.96).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.88 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000519006.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
NAT1	NM_000662.8	MANE Select	c.-86+1146T>C	intron	N/A	NP_000653.3
NAT1	NM_001160175.4		c.-34T>C	5_prime_UTR	Exon 2 of 5	NP_001153647.1
NAT1	NM_001160170.4		c.-486T>C	5_prime_UTR	Exon 2 of 5	NP_001153642.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
NAT1	ENST00000519006.5	TSL:1	n.42T>C	non_coding_transcript_exon	Exon 1 of 4
NAT1	ENST00000307719.9	TSL:1 MANE Select	c.-86+1146T>C	intron	N/A	ENSP00000307218.4
NAT1	ENST00000518029.5	TSL:1	c.-469-1065T>C	intron	N/A	ENSP00000428270.1

Frequencies

GnomAD3 genomes

AF:

0.725

AC:

110258

AN:

152004

Hom.:

40758

Cov.:

show subpopulations

Gnomad AFR

AF:

0.888

Gnomad AMI

AF:

0.545

Gnomad AMR

AF:

0.661

Gnomad ASJ

AF:

0.674

Gnomad EAS

AF:

0.623

Gnomad SAS

AF:

0.626

Gnomad FIN

AF:

0.708

Gnomad MID

AF:

0.741

Gnomad NFE

AF:

0.664

Gnomad OTH

AF:

0.711

GnomAD4 exome

AF:

0.650

AC:

AN:

Hom.:

Cov.:

AF XY:

0.660

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

1.00

AC:

AN:

Middle Eastern (MID)

AF:

1.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.635

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

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:

0.726

AC:

110376

AN:

152122

Hom.:

40816

Cov.:

AF XY:

0.722

AC XY:

53694

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.888

AC:

36843

AN:

41508

American (AMR)

AF:

0.661

AC:

10104

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.674

AC:

2340

AN:

3470

East Asian (EAS)

AF:

0.622

AC:

3210

AN:

5162

South Asian (SAS)

AF:

0.627

AC:

3026

AN:

4830

European-Finnish (FIN)

AF:

0.708

AC:

7477

AN:

10568

Middle Eastern (MID)

AF:

0.745

AC:

219

AN:

294

European-Non Finnish (NFE)

AF:

0.664

AC:

45163

AN:

67998

Other (OTH)

AF:

0.712

AC:

1499

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1502

3004

4505

6007

7509

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

834

1668

2502

3336

4170

<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:

0.688

Hom.:

106812

Bravo

AF:

0.729

Asia WGS

AF:

0.650

AC:

2262

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

0.058

(source)

DANN

Benign

0.43

PhyloP100

-1.9

PromoterAI

-0.016

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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