rs8190870

Variant names:

• chr8-18223763-C-T
• rs8190870
• NM_000662.8:c.*843C>T

Variant summary

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

The NM_000662.8(NAT1):​c.*843C>T variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 152,228 control chromosomes in the GnomAD database, including 2,267 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 0.16 (2253 hom., cov: 31)
  • Exomes 𝑓: 0.17 (14 hom.)
• Consequence: NAT1 NM_000662.8 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12
• Publications: 7 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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000662.8. 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_000662.8	MANE Select	c.*843C>T		downstream_gene	N/A	NP_000653.3
	NAT1	NM_001160175.4		c.*843C>T		downstream_gene	N/A	NP_001153647.1
	NAT1	NM_001160176.4		c.*843C>T		downstream_gene	N/A	NP_001153648.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAT1	ENST00000307719.9	TSL:1 MANE Select	c.*843C>T		downstream_gene	N/A	ENSP00000307218.4
	NAT1	ENST00000518029.5	TSL:1	c.*843C>T		downstream_gene	N/A	ENSP00000428270.1
	NAT1	ENST00000545197.3	TSL:5	c.*843C>T		downstream_gene	N/A	ENSP00000443194.1

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24590 AN: 151362 Hom.: 2246 Cov.: 31

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.0999

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.0199

Gnomad SAS AF: 0.148

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.139

GnomAD4 exome AF: 0.169 AC: 126 AN: 744 Hom.: 14 AF XY: 0.184 AC XY: 79 AN XY: 430

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.171 AC: 124 AN: 726

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.200 AC: 2 AN: 10

Other (OTH) AF: 0.00 AC: 0 AN: 6

GnomAD4 genome AF: 0.163 AC: 24625 AN: 151484 Hom.: 2253 Cov.: 31 AF XY: 0.162 AC XY: 11965 AN XY: 74008

African (AFR) AF: 0.233 AC: 9604 AN: 41248

American (AMR) AF: 0.0997 AC: 1519 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 534 AN: 3464

East Asian (EAS) AF: 0.0195 AC: 101 AN: 5176

South Asian (SAS) AF: 0.149 AC: 711 AN: 4778

European-Finnish (FIN) AF: 0.203 AC: 2107 AN: 10380

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.140 AC: 9526 AN: 67886

Other (OTH) AF: 0.139 AC: 292 AN: 2108

Alfa AF: 0.149 Hom.: 3967

Bravo AF: 0.158

Asia WGS AF: 0.0990 AC: 345 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.66
DANN	Benign	0.22
PhyloP100		-1.1
Mutation Taster		=93/7	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs8190870; hg19: chr8-18081272;