rs8190852

Variant names:

• chr8-18221360-C-G
• rs8190852
• NM_000662.8:c.-6-682C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000662.8(NAT1):​c.-6-682C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0179 in 148,962 control chromosomes in the GnomAD database, including 47 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 0.018 (47 hom., cov: 31)
• Consequence: NAT1 NM_000662.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0140
• Publications: 1 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=-1.03).
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0179 (2662/148962) while in subpopulation SAS AF = 0.0357 (168/4708). AF 95% confidence interval is 0.0313. There are 47 homozygotes in GnomAd4. There are 1238 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2662 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAT1	NM_000662.8	c.-6-682C>G		intron_variant	Intron 2 of 2	ENST00000307719.9	NP_000653.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAT1	ENST00000307719.9	c.-6-682C>G		intron_variant	Intron 2 of 2	1	NM_000662.8	ENSP00000307218.4

Frequencies

GnomAD3 genomes AF: 0.0178 AC: 2655 AN: 148856 Hom.: 47 Cov.: 31

Gnomad AFR AF: 0.00462

Gnomad AMI AF: 0.0813

Gnomad AMR AF: 0.0146

Gnomad ASJ AF: 0.0414

Gnomad EAS AF: 0.00590

Gnomad SAS AF: 0.0352

Gnomad FIN AF: 0.00796

Gnomad MID AF: 0.0817

Gnomad NFE AF: 0.0251

Gnomad OTH AF: 0.0220

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

GnomAD4 genome AF: 0.0179 AC: 2662 AN: 148962 Hom.: 47 Cov.: 31 AF XY: 0.0171 AC XY: 1238 AN XY: 72452

African (AFR) AF: 0.00465 AC: 188 AN: 40388

American (AMR) AF: 0.0145 AC: 217 AN: 14924

Ashkenazi Jewish (ASJ) AF: 0.0414 AC: 143 AN: 3450

East Asian (EAS) AF: 0.00591 AC: 30 AN: 5076

South Asian (SAS) AF: 0.0357 AC: 168 AN: 4708

European-Finnish (FIN) AF: 0.00796 AC: 77 AN: 9668

Middle Eastern (MID) AF: 0.0868 AC: 25 AN: 288

European-Non Finnish (NFE) AF: 0.0251 AC: 1694 AN: 67482

Other (OTH) AF: 0.0222 AC: 46 AN: 2068

Alfa AF: 0.0214 Hom.: 3

Bravo AF: 0.0174

Asia WGS AF: 0.0180 AC: 62 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.4
DANN	Benign	0.44
PhyloP100		0.014
PromoterAI		0.010	Neutral
Mutation Taster		=100/0	polymorphism

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: rs8190852; hg19: chr8-18078869;