chr8-18396957-T-C

Position:

• chr8-18396957-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000015.3(NAT2):​c.-6-3041T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0935 in 152,246 control chromosomes in the GnomAD database, including 910 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 0.094 (910 hom., cov: 33)
• Consequence: NAT2 NM_000015.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.295

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.133 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NAT2	NM_000015.3	c.-6-3041T>C		intron_variant		ENST00000286479.4
NAT2	XM_017012938.2	c.-6-3041T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAT2	ENST00000286479.4	c.-6-3041T>C		intron_variant		1	NM_000015.3	P1
NAT2	ENST00000520116.1	c.-57-3380T>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.0936 AC: 14242 AN: 152128 Hom.: 910 Cov.: 33

Gnomad AFR AF: 0.0251

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0286

Gnomad FIN AF: 0.120

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.137

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0935 AC: 14238 AN: 152246 Hom.: 910 Cov.: 33 AF XY: 0.0907 AC XY: 6752 AN XY: 74452

Gnomad4 AFR AF: 0.0250

Gnomad4 AMR AF: 0.102

Gnomad4 ASJ AF: 0.178

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0284

Gnomad4 FIN AF: 0.120

Gnomad4 NFE AF: 0.135

Gnomad4 OTH AF: 0.136

Alfa AF: 0.135 Hom.: 1458

Bravo AF: 0.0913

Asia WGS AF: 0.0140 AC: 49 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.7
DANN	Benign	0.72

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

LitVar

Other links and lift over

dbSNP: rs2410556; hg19: chr8-18254467;