Genetic Variant XM_017012938.2:c.-7+4115A>G (chr8-18391151-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The XM_017012938.2(NAT2):c.-7+4115A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 152,028 control chromosomes in the GnomAD database, including 4,513 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 0.23 ( 4513 hom., cov: 31)

Exomes 𝑓: 0.091 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

NAT2
XM_017012938.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.309

Publications

20 publications found

Variant links:

Genes affected

NAT2 (HGNC:7646): (N-acetyltransferase 2) This gene encodes an enzyme that functions to both activate and deactivate arylamine and hydrazine drugs and carcinogens. Polymorphisms in this gene are responsible for the N-acetylation polymorphism in which human populations segregate into rapid, intermediate, and slow acetylator phenotypes. Polymorphisms in this gene are also associated with higher incidences of cancer and drug toxicity. A second polymorphic arylamine N-acetyltransferase gene (NAT1), is located near this gene (NAT2). [provided by RefSeq, Sep 2019]

NAT2 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=-0.9).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.468 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000286479.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAT2	NM_000015.3	MANE Select	c.-201A>G		upstream_gene	N/A	NP_000006.2	P11245

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NAT2	ENST00000286479.4	TSL:1 MANE Select	c.-201A>G	upstream_gene	N/A	ENSP00000286479.3	P11245
NAT2	ENST00000893781.1		c.-304A>G	upstream_gene	N/A	ENSP00000563840.1
NAT2	ENST00000893782.1		c.-378A>G	upstream_gene	N/A	ENSP00000563841.1

Frequencies

GnomAD3 genomes

AF:

0.232

AC:

35221

AN:

151910

Hom.:

4514

Cov.:

show subpopulations

Gnomad AFR

AF:

0.296

Gnomad AMI

AF:

0.161

Gnomad AMR

AF:

0.258

Gnomad ASJ

AF:

0.108

Gnomad EAS

AF:

0.485

Gnomad SAS

AF:

0.171

Gnomad FIN

AF:

0.226

Gnomad MID

AF:

0.139

Gnomad NFE

AF:

0.182

Gnomad OTH

AF:

0.198

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0909

AC:

AN:

Hom.:

AF XY:

0.111

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)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0909

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.232

AC:

35251

AN:

152028

Hom.:

4513

Cov.:

AF XY:

0.234

AC XY:

17366

AN XY:

74300

show subpopulations

African (AFR)

AF:

0.296

AC:

12282

AN:

41476

American (AMR)

AF:

0.258

AC:

3938

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.108

AC:

376

AN:

3468

East Asian (EAS)

AF:

0.484

AC:

2479

AN:

5120

South Asian (SAS)

AF:

0.172

AC:

830

AN:

4814

European-Finnish (FIN)

AF:

0.226

AC:

2394

AN:

10592

Middle Eastern (MID)

AF:

0.126

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.182

AC:

12343

AN:

67976

Other (OTH)

AF:

0.202

AC:

425

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1324

2647

3971

5294

6618

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

370

740

1110

1480

1850

<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:

0.191

Hom.:

3602

Bravo

AF:

0.241

Asia WGS

AF:

0.307

AC:

1071

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

2.7

(source)

DANN

Benign

0.57

PhyloP100

0.31

PromoterAI

0.086

Neutral

(source)

Splicing

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over