chr8-18221119-G-A

Position:

• chr8-18221119-G-A

Variant summary

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

The NM_000662.8(NAT1):​c.-6-923G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 151,990 control chromosomes in the GnomAD database, including 4,639 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 0.21 (4639 hom., cov: 32)
• Consequence: NAT1 NM_000662.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.393

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

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 = 0.399 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NAT1	NM_000662.8	c.-6-923G>A		intron_variant		ENST00000307719.9	NP_000653.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NAT1	ENST00000307719.9	c.-6-923G>A		intron_variant		1	NM_000662.8	ENSP00000307218	P1

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32602 AN: 151874 Hom.: 4620 Cov.: 32

Gnomad AFR AF: 0.403

Gnomad AMI AF: 0.205

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.0726

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.208

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.182

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

GnomAD4 genome AF: 0.215 AC: 32664 AN: 151990 Hom.: 4639 Cov.: 32 AF XY: 0.213 AC XY: 15845 AN XY: 74304

Gnomad4 AFR AF: 0.404

Gnomad4 AMR AF: 0.118

Gnomad4 ASJ AF: 0.155

Gnomad4 EAS AF: 0.0724

Gnomad4 SAS AF: 0.154

Gnomad4 FIN AF: 0.208

Gnomad4 NFE AF: 0.142

Gnomad4 OTH AF: 0.186

Alfa AF: 0.157 Hom.: 2233

Bravo AF: 0.215

Asia WGS AF: 0.134 AC: 467 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.10
DANN	Benign	0.56

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

Publications

LitVar

Other links and lift over

dbSNP: rs8190845; hg19: chr8-18078628;