chr8-18221363-T-C

Variant names:

• chr8-18221363-T-C
• rs8190853
• NM_000662.8:c.-6-679T>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.-6-679T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0175 in 151,576 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: 0.213
• 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=-1.02).
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0175 (2660/151576) while in subpopulation SAS AF = 0.0353 (169/4788). AF 95% confidence interval is 0.031. There are 47 homozygotes in GnomAd4. There are 1239 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2660 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAT1	NM_000662.8	c.-6-679T>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.-6-679T>C		intron_variant	Intron 2 of 2	1	NM_000662.8	ENSP00000307218.4

Frequencies

GnomAD3 genomes AF: 0.0175 AC: 2653 AN: 151464 Hom.: 47 Cov.: 31

Gnomad AFR AF: 0.00449

Gnomad AMI AF: 0.0811

Gnomad AMR AF: 0.0142

Gnomad ASJ AF: 0.0417

Gnomad EAS AF: 0.00581

Gnomad SAS AF: 0.0348

Gnomad FIN AF: 0.00745

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0249

Gnomad OTH AF: 0.0216

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

GnomAD4 genome AF: 0.0175 AC: 2660 AN: 151576 Hom.: 47 Cov.: 31 AF XY: 0.0167 AC XY: 1239 AN XY: 74050

African (AFR) AF: 0.00452 AC: 187 AN: 41362

American (AMR) AF: 0.0142 AC: 216 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.0417 AC: 144 AN: 3456

East Asian (EAS) AF: 0.00582 AC: 30 AN: 5154

South Asian (SAS) AF: 0.0353 AC: 169 AN: 4788

European-Finnish (FIN) AF: 0.00745 AC: 78 AN: 10466

Middle Eastern (MID) AF: 0.0856 AC: 25 AN: 292

European-Non Finnish (NFE) AF: 0.0249 AC: 1691 AN: 67826

Other (OTH) AF: 0.0219 AC: 46 AN: 2102

Alfa AF: 0.0249 Hom.: 86

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	2.8
DANN	Benign	0.68
PhyloP100		0.21
PromoterAI		-0.0020	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: rs8190853; hg19: chr8-18078872;