8-18197877-A-C

Variant names:

• chr8-18197877-A-C
• rs7388368
• NM_001291962.2:c.-192-11904A>C

Variant summary

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

The NM_001291962.2(NAT1):​c.-192-11904A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.792 in 151,262 control chromosomes in the GnomAD database, including 47,760 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 0.79 (47760 hom., cov: 28)
• Consequence: NAT1 NM_001291962.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.639
• Publications: 3 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.866 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001291962.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAT1	NM_001291962.2		c.-192-11904A>C		intron	N/A	NP_001278891.1
	NAT1	NM_001160179.3		c.-260-11904A>C		intron	N/A	NP_001153651.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAT1	ENST00000517441.5	TSL:2	n.93-11904A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.792 AC: 119664 AN: 151160 Hom.: 47728 Cov.: 28

Gnomad AFR AF: 0.875

Gnomad AMI AF: 0.764

Gnomad AMR AF: 0.743

Gnomad ASJ AF: 0.781

Gnomad EAS AF: 0.595

Gnomad SAS AF: 0.670

Gnomad FIN AF: 0.766

Gnomad MID AF: 0.869

Gnomad NFE AF: 0.780

Gnomad OTH AF: 0.799

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

GnomAD4 genome AF: 0.792 AC: 119739 AN: 151262 Hom.: 47760 Cov.: 28 AF XY: 0.786 AC XY: 58009 AN XY: 73842

African (AFR) AF: 0.874 AC: 36029 AN: 41222

American (AMR) AF: 0.744 AC: 11320 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.781 AC: 2713 AN: 3472

East Asian (EAS) AF: 0.594 AC: 3049 AN: 5130

South Asian (SAS) AF: 0.670 AC: 3218 AN: 4800

European-Finnish (FIN) AF: 0.766 AC: 7880 AN: 10282

Middle Eastern (MID) AF: 0.877 AC: 256 AN: 292

European-Non Finnish (NFE) AF: 0.780 AC: 52908 AN: 67838

Other (OTH) AF: 0.797 AC: 1671 AN: 2096

Alfa AF: 0.779 Hom.: 8734

Bravo AF: 0.795

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.1
DANN	Benign	0.43
PhyloP100		0.64
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7388368; hg19: chr8-18055386; COSMIC: COSV72832002;