chr8-18218397-T-A

Position:

• chr8-18218397-T-A

Variant summary

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

The ENST00000307719.9(NAT1):​c.-85-1014T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.674 in 151,964 control chromosomes in the GnomAD database, including 35,273 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 0.67 (35273 hom., cov: 31)
• Consequence: NAT1 ENST00000307719.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.308

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.755 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NAT1	NM_000662.8	c.-85-1014T>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.-85-1014T>A		intron_variant		1	NM_000662.8	ENSP00000307218	P1

Frequencies

GnomAD3 genomes AF: 0.675 AC: 102438 AN: 151844 Hom.: 35256 Cov.: 31

Gnomad AFR AF: 0.564

Gnomad AMI AF: 0.819

Gnomad AMR AF: 0.640

Gnomad ASJ AF: 0.720

Gnomad EAS AF: 0.467

Gnomad SAS AF: 0.609

Gnomad FIN AF: 0.708

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.761

Gnomad OTH AF: 0.680

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

GnomAD4 genome AF: 0.674 AC: 102498 AN: 151964 Hom.: 35273 Cov.: 31 AF XY: 0.669 AC XY: 49666 AN XY: 74274

Gnomad4 AFR AF: 0.564

Gnomad4 AMR AF: 0.640

Gnomad4 ASJ AF: 0.720

Gnomad4 EAS AF: 0.467

Gnomad4 SAS AF: 0.611

Gnomad4 FIN AF: 0.708

Gnomad4 NFE AF: 0.761

Gnomad4 OTH AF: 0.674

Alfa AF: 0.709 Hom.: 4842

Bravo AF: 0.665

Asia WGS AF: 0.538 AC: 1873 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.2
DANN	Benign	0.80

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: rs4921880; hg19: chr8-18075906;