rs4986989

Positions:

• chr8-18222008-A-T

Variant summary

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

The NM_000662.8(NAT1):​c.-6-34A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0214 in 1,565,808 control chromosomes in the GnomAD database, including 454 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 (49 hom., cov: 32)
  • Exomes 𝑓: 0.022 (405 hom.)
• Consequence: NAT1 NM_000662.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.102

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=-0.96).
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.074 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NAT1	NM_000662.8	c.-6-34A>T		intron_variant		ENST00000307719.9	NP_000653.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NAT1	ENST00000307719.9	c.-6-34A>T		intron_variant		1	NM_000662.8	ENSP00000307218	P1

Frequencies

GnomAD3 genomes AF: 0.0181 AC: 2751 AN: 152212 Hom.: 49 Cov.: 32

Gnomad AFR AF: 0.00487

Gnomad AMI AF: 0.0811

Gnomad AMR AF: 0.0147

Gnomad ASJ AF: 0.0421

Gnomad EAS AF: 0.00653

Gnomad SAS AF: 0.0358

Gnomad FIN AF: 0.00877

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0255

Gnomad OTH AF: 0.0225

GnomAD3 exomes AF: 0.0204 AC: 4363 AN: 214154 Hom.: 67 AF XY: 0.0217 AC XY: 2492 AN XY: 114790

Gnomad AFR exome AF: 0.00381

Gnomad AMR exome AF: 0.0116

Gnomad ASJ exome AF: 0.0449

Gnomad EAS exome AF: 0.00787

Gnomad SAS exome AF: 0.0294

Gnomad FIN exome AF: 0.00869

Gnomad NFE exome AF: 0.0257

Gnomad OTH exome AF: 0.0294

GnomAD4 exome AF: 0.0218 AC: 30751 AN: 1413478 Hom.: 405 Cov.: 31 AF XY: 0.0223 AC XY: 15555 AN XY: 698222

Gnomad4 AFR exome AF: 0.00510

Gnomad4 AMR exome AF: 0.0118

Gnomad4 ASJ exome AF: 0.0453

Gnomad4 EAS exome AF: 0.00588

Gnomad4 SAS exome AF: 0.0273

Gnomad4 FIN exome AF: 0.00951

Gnomad4 NFE exome AF: 0.0223

Gnomad4 OTH exome AF: 0.0272

GnomAD4 genome AF: 0.0181 AC: 2759 AN: 152330 Hom.: 49 Cov.: 32 AF XY: 0.0174 AC XY: 1297 AN XY: 74482

Gnomad4 AFR AF: 0.00491

Gnomad4 AMR AF: 0.0147

Gnomad4 ASJ AF: 0.0421

Gnomad4 EAS AF: 0.00654

Gnomad4 SAS AF: 0.0365

Gnomad4 FIN AF: 0.00877

Gnomad4 NFE AF: 0.0255

Gnomad4 OTH AF: 0.0227

Alfa AF: 0.0269 Hom.: 46

Bravo AF: 0.0174

Asia WGS AF: 0.0240 AC: 83 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	3.4
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: rs4986989; hg19: chr8-18079517;