NM_000662.8:c.-86+385A>G

Variant names:

• chr8-18210565-A-G
• rs7017402
• NM_000662.8:c.-86+385A>G

Variant summary

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

The NM_000662.8(NAT1):​c.-86+385A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.808 in 152,172 control chromosomes in the GnomAD database, including 50,477 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 0.81 (50477 hom., cov: 32)
• Consequence: NAT1 NM_000662.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.882 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAT1	NM_000662.8	c.-86+385A>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.-86+385A>G		intron_variant	Intron 1 of 2	1	NM_000662.8	ENSP00000307218.4
NAT1	ENST00000518029.5	c.-470+385A>G		intron_variant	Intron 1 of 3	1		ENSP00000428270.1
NAT1	ENST00000517441.5	n.267+610A>G		intron_variant	Intron 3 of 4	2
NAT1	ENST00000517574.5	n.47+385A>G		intron_variant	Intron 1 of 3	3

Frequencies

GnomAD3 genomes AF: 0.808 AC: 122872 AN: 152054 Hom.: 50458 Cov.: 32

Gnomad AFR AF: 0.685

Gnomad AMI AF: 0.933

Gnomad AMR AF: 0.763

Gnomad ASJ AF: 0.896

Gnomad EAS AF: 0.610

Gnomad SAS AF: 0.764

Gnomad FIN AF: 0.919

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.888

Gnomad OTH AF: 0.816

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

GnomAD4 genome AF: 0.808 AC: 122941 AN: 152172 Hom.: 50477 Cov.: 32 AF XY: 0.806 AC XY: 59966 AN XY: 74396

African (AFR) AF: 0.685 AC: 28410 AN: 41474

American (AMR) AF: 0.763 AC: 11671 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.896 AC: 3110 AN: 3472

East Asian (EAS) AF: 0.609 AC: 3148 AN: 5168

South Asian (SAS) AF: 0.764 AC: 3680 AN: 4814

European-Finnish (FIN) AF: 0.919 AC: 9759 AN: 10620

Middle Eastern (MID) AF: 0.769 AC: 226 AN: 294

European-Non Finnish (NFE) AF: 0.887 AC: 60364 AN: 68018

Other (OTH) AF: 0.816 AC: 1724 AN: 2112

Alfa AF: 0.853 Hom.: 102201

Bravo AF: 0.792

Asia WGS AF: 0.678 AC: 2362 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.9
DANN	Benign	0.44
PhyloP100		-1.2
PromoterAI		0.018	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7017402; hg19: chr8-18068074;