rs8190848

Variant names:

• chr8-18221222-T-C
• rs8190848
• NM_000662.8:c.-6-820T>C

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.-6-820T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0181 in 152,232 control chromosomes in the GnomAD database, including 49 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 (49 hom., cov: 32)
• Consequence: NAT1 NM_000662.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.122
• 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=-0.98).
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0181 (2755/152232) while in subpopulation SAS AF = 0.0362 (174/4812). AF 95% confidence interval is 0.0318. There are 49 homozygotes in GnomAd4. There are 1294 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2755 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAT1	NM_000662.8	c.-6-820T>C		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.-6-820T>C		intron_variant	Intron 2 of 2	1	NM_000662.8	ENSP00000307218.4

Frequencies

GnomAD3 genomes AF: 0.0181 AC: 2747 AN: 152116 Hom.: 49 Cov.: 32

Gnomad AFR AF: 0.00483

Gnomad AMI AF: 0.0811

Gnomad AMR AF: 0.0147

Gnomad ASJ AF: 0.0421

Gnomad EAS AF: 0.00655

Gnomad SAS AF: 0.0355

Gnomad FIN AF: 0.00859

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0255

Gnomad OTH AF: 0.0229

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

GnomAD4 genome AF: 0.0181 AC: 2755 AN: 152232 Hom.: 49 Cov.: 32 AF XY: 0.0174 AC XY: 1294 AN XY: 74428

African (AFR) AF: 0.00486 AC: 202 AN: 41560

American (AMR) AF: 0.0147 AC: 224 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0421 AC: 146 AN: 3472

East Asian (EAS) AF: 0.00656 AC: 34 AN: 5180

South Asian (SAS) AF: 0.0362 AC: 174 AN: 4812

European-Finnish (FIN) AF: 0.00859 AC: 91 AN: 10588

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0255 AC: 1736 AN: 68018

Other (OTH) AF: 0.0232 AC: 49 AN: 2114

Alfa AF: 0.0252 Hom.: 89

Bravo AF: 0.0174

Asia WGS AF: 0.0240 AC: 83 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.4
DANN	Benign	0.57
PhyloP100		0.12
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: rs8190848; hg19: chr8-18078731;