chr8-18208617-T-C

Position:

• chr8-18208617-T-C

Variant summary

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

The NM_001291962.2(NAT1):​c.-192-1164T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.477 in 152,108 control chromosomes in the GnomAD database, including 19,211 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 0.48 (19211 hom., cov: 33)
• Consequence: NAT1 NM_001291962.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.474

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.586 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NAT1	NM_001160179.3	c.-260-1164T>C		intron_variant
NAT1	NM_001291962.2	c.-192-1164T>C		intron_variant
NAT1	XM_047422397.1	c.-815-1164T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAT1	ENST00000517441.5	n.93-1164T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.478 AC: 72583 AN: 151990 Hom.: 19211 Cov.: 33

Gnomad AFR AF: 0.236

Gnomad AMI AF: 0.547

Gnomad AMR AF: 0.494

Gnomad ASJ AF: 0.591

Gnomad EAS AF: 0.503

Gnomad SAS AF: 0.448

Gnomad FIN AF: 0.617

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.591

Gnomad OTH AF: 0.511

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

GnomAD4 genome AF: 0.477 AC: 72604 AN: 152108 Hom.: 19211 Cov.: 33 AF XY: 0.477 AC XY: 35442 AN XY: 74354

Gnomad4 AFR AF: 0.236

Gnomad4 AMR AF: 0.494

Gnomad4 ASJ AF: 0.591

Gnomad4 EAS AF: 0.503

Gnomad4 SAS AF: 0.448

Gnomad4 FIN AF: 0.617

Gnomad4 NFE AF: 0.591

Gnomad4 OTH AF: 0.512

Alfa AF: 0.573 Hom.: 46625

Bravo AF: 0.459

Asia WGS AF: 0.437 AC: 1520 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.4
DANN	Benign	0.49

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10888150; hg19: chr8-18066126;