8-18210565-A-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.83).
• 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/exons	MANE	UniProt
NAT1	NM_000662.8	c.-86+385A>G		intron_variant		ENST00000307719.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAT1	ENST00000307719.9	c.-86+385A>G		intron_variant		1	NM_000662.8	P1
NAT1	ENST00000518029.5	c.-470+385A>G		intron_variant		1		P1
NAT1	ENST00000517441.5	n.267+610A>G		intron_variant, non_coding_transcript_variant		2
NAT1	ENST00000517574.5	n.47+385A>G		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.685

Gnomad4 AMR AF: 0.763

Gnomad4 ASJ AF: 0.896

Gnomad4 EAS AF: 0.609

Gnomad4 SAS AF: 0.764

Gnomad4 FIN AF: 0.919

Gnomad4 NFE AF: 0.887

Gnomad4 OTH AF: 0.816

Alfa AF: 0.866 Hom.: 26426

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

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: rs7017402; hg19: chr8-18068074;