8-18214398-A-G

Variant names:

• chr8-18214398-A-G
• rs13253389
• NM_000662.8:c.-86+4218A>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+4218A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.538 in 151,984 control chromosomes in the GnomAD database, including 24,109 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 0.54 (24109 hom., cov: 32)
• Consequence: NAT1 NM_000662.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.774
• Publications: 12 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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.665 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAT1	NM_000662.8	c.-86+4218A>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+4218A>G		intron_variant	Intron 1 of 2	1	NM_000662.8	ENSP00000307218.4

Frequencies

GnomAD3 genomes AF: 0.539 AC: 81781 AN: 151864 Hom.: 24111 Cov.: 32

Gnomad AFR AF: 0.310

Gnomad AMI AF: 0.693

Gnomad AMR AF: 0.527

Gnomad ASJ AF: 0.659

Gnomad EAS AF: 0.373

Gnomad SAS AF: 0.440

Gnomad FIN AF: 0.677

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.670

Gnomad OTH AF: 0.552

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

GnomAD4 genome AF: 0.538 AC: 81793 AN: 151984 Hom.: 24109 Cov.: 32 AF XY: 0.534 AC XY: 39649 AN XY: 74286

African (AFR) AF: 0.310 AC: 12836 AN: 41432

American (AMR) AF: 0.526 AC: 8040 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.659 AC: 2286 AN: 3470

East Asian (EAS) AF: 0.373 AC: 1923 AN: 5154

South Asian (SAS) AF: 0.440 AC: 2116 AN: 4812

European-Finnish (FIN) AF: 0.677 AC: 7148 AN: 10562

Middle Eastern (MID) AF: 0.466 AC: 137 AN: 294

European-Non Finnish (NFE) AF: 0.670 AC: 45515 AN: 67962

Other (OTH) AF: 0.550 AC: 1161 AN: 2112

Alfa AF: 0.619 Hom.: 123102

Bravo AF: 0.518

Asia WGS AF: 0.385 AC: 1344 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	8.2
DANN	Benign	0.69
PhyloP100		-0.77
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: rs13253389; hg19: chr8-18071907; COSMIC: COSV56985750; COSMIC: COSV56985750;