8-18216433-A-G

Variant names:

• chr8-18216433-A-G
• rs6586714
• NM_000662.8:c.-85-2978A>G

Variant summary

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

The NM_000662.8(NAT1):​c.-85-2978A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.842 in 152,076 control chromosomes in the GnomAD database, including 54,425 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 0.84 (54425 hom., cov: 31)
• Consequence: NAT1 NM_000662.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.319

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]

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 (EAS) allele frequency at 95% confidence interval = 0.894 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAT1	NM_000662.8	c.-85-2978A>G		intron_variant	Intron 1 of 2	ENST00000307719.9	NP_000653.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAT1	ENST00000307719.9	c.-85-2978A>G		intron_variant	Intron 1 of 2	1	NM_000662.8	ENSP00000307218.4

Frequencies

GnomAD3 genomes AF: 0.842 AC: 127945 AN: 151958 Hom.: 54409 Cov.: 31

Gnomad AFR AF: 0.726

Gnomad AMI AF: 0.834

Gnomad AMR AF: 0.880

Gnomad ASJ AF: 0.938

Gnomad EAS AF: 0.914

Gnomad SAS AF: 0.805

Gnomad FIN AF: 0.814

Gnomad MID AF: 0.873

Gnomad NFE AF: 0.900

Gnomad OTH AF: 0.873

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

GnomAD4 genome AF: 0.842 AC: 128013 AN: 152076 Hom.: 54425 Cov.: 31 AF XY: 0.838 AC XY: 62312 AN XY: 74344

Gnomad4 AFR AF: 0.726

Gnomad4 AMR AF: 0.880

Gnomad4 ASJ AF: 0.938

Gnomad4 EAS AF: 0.914

Gnomad4 SAS AF: 0.805

Gnomad4 FIN AF: 0.814

Gnomad4 NFE AF: 0.900

Gnomad4 OTH AF: 0.870

Alfa AF: 0.863 Hom.: 11061

Bravo AF: 0.843

Asia WGS AF: 0.832 AC: 2893 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.7
DANN	Benign	0.40

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: rs6586714; hg19: chr8-18073942;