chr8-18198075-T-A

Position:

• chr8-18198075-T-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001291962.2(NAT1):​c.-192-11706T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.766 in 152,006 control chromosomes in the GnomAD database, including 44,986 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 0.77 (44986 hom., cov: 30)
• Consequence: NAT1 NM_001291962.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.494

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]

NAT1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.859 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NAT1	NM_001291962.2	c.-192-11706T>A		intron_variant			NP_001278891.1
NAT1	NM_001160179.3	c.-260-11706T>A		intron_variant			NP_001153651.1
NAT1	XM_047422397.1	c.-815-11706T>A		intron_variant			XP_047278353.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NAT1	ENST00000517441.5	n.93-11706T>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.766 AC: 116306 AN: 151888 Hom.: 44944 Cov.: 30

Gnomad AFR AF: 0.867

Gnomad AMI AF: 0.603

Gnomad AMR AF: 0.720

Gnomad ASJ AF: 0.724

Gnomad EAS AF: 0.592

Gnomad SAS AF: 0.639

Gnomad FIN AF: 0.760

Gnomad MID AF: 0.820

Gnomad NFE AF: 0.741

Gnomad OTH AF: 0.772

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

GnomAD4 genome AF: 0.766 AC: 116401 AN: 152006 Hom.: 44986 Cov.: 30 AF XY: 0.761 AC XY: 56564 AN XY: 74302

Gnomad4 AFR AF: 0.867

Gnomad4 AMR AF: 0.721

Gnomad4 ASJ AF: 0.724

Gnomad4 EAS AF: 0.592

Gnomad4 SAS AF: 0.640

Gnomad4 FIN AF: 0.760

Gnomad4 NFE AF: 0.741

Gnomad4 OTH AF: 0.770

Alfa AF: 0.753 Hom.: 5388

Bravo AF: 0.767

Asia WGS AF: 0.635 AC: 2209 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.6
DANN	Benign	0.63

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4921877; hg19: chr8-18055584;