XM_017012938.2:c.-7+4115A>G

Variant names:

• chr8-18391151-A-G
• rs4646246
• XM_017012938.2:c.-7+4115A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.309
• Publications: 20 publications found

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]

ACMG classification

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAT2	XM_017012938.2	c.-7+4115A>G		intron_variant	Intron 2 of 2		XP_016868427.1
NAT2	NM_000015.3	c.-201A>G		upstream_gene_variant		ENST00000286479.4	NP_000006.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAT2	ENST00000286479.4	c.-201A>G		upstream_gene_variant		1	NM_000015.3	ENSP00000286479.3
NAT2	ENST00000520116.1	c.-252A>G		upstream_gene_variant		3		ENSP00000428416.1

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35221 AN: 151910 Hom.: 4514 Cov.: 31

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: 2 AN: 22 Hom.: 0 AF XY: 0.111 AC XY: 2 AN XY: 18

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0909 AC: 2 AN: 22

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.232 AC: 35251 AN: 152028 Hom.: 4513 Cov.: 31 AF XY: 0.234 AC XY: 17366 AN XY: 74300

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: 37 AN: 294

European-Non Finnish (NFE) AF: 0.182 AC: 12343 AN: 67976

Other (OTH) AF: 0.202 AC: 425 AN: 2108

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.7
DANN	Benign	0.57
PhyloP100		0.31
PromoterAI		0.086	Neutral

Splicing

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

Other links and lift over

dbSNP: rs4646246; hg19: chr8-18248661;