rs4986990

Positions:

• chr8-18222506-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_000662.8(NAT1):​c.459G>A​(p.Thr153Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0215 in 1,613,978 control chromosomes in the GnomAD database, including 485 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 (436 hom.)
• Consequence: NAT1 NM_000662.8 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.751

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP7: Synonymous conserved (PhyloP=-0.751 with no splicing effect.
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0741 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NAT1	NM_000662.8	c.459G>A	p.Thr153Thr	synonymous_variant	3/3	ENST00000307719.9	NP_000653.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NAT1	ENST00000307719.9	c.459G>A	p.Thr153Thr	synonymous_variant	3/3	1	NM_000662.8	ENSP00000307218.4

Frequencies

GnomAD3 genomes AF: 0.0181 AC: 2757 AN: 152036 Hom.: 49 Cov.: 32

Gnomad AFR AF: 0.00491

Gnomad AMI AF: 0.0813

Gnomad AMR AF: 0.0148

Gnomad ASJ AF: 0.0421

Gnomad EAS AF: 0.00674

Gnomad SAS AF: 0.0357

Gnomad FIN AF: 0.00887

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0255

Gnomad OTH AF: 0.0229

GnomAD3 exomes AF: 0.0203 AC: 5107 AN: 251132 Hom.: 81 AF XY: 0.0217 AC XY: 2945 AN XY: 135706

Gnomad AFR exome AF: 0.00381

Gnomad AMR exome AF: 0.0112

Gnomad ASJ exome AF: 0.0426

Gnomad EAS exome AF: 0.00794

Gnomad SAS exome AF: 0.0275

Gnomad FIN exome AF: 0.00864

Gnomad NFE exome AF: 0.0253

Gnomad OTH exome AF: 0.0289

GnomAD4 exome AF: 0.0218 AC: 31925 AN: 1461824 Hom.: 436 Cov.: 32 AF XY: 0.0224 AC XY: 16291 AN XY: 727228

Gnomad4 AFR exome AF: 0.00505

Gnomad4 AMR exome AF: 0.0115

Gnomad4 ASJ exome AF: 0.0445

Gnomad4 EAS exome AF: 0.00587

Gnomad4 SAS exome AF: 0.0270

Gnomad4 FIN exome AF: 0.00957

Gnomad4 NFE exome AF: 0.0224

Gnomad4 OTH exome AF: 0.0270

GnomAD4 genome AF: 0.0182 AC: 2765 AN: 152154 Hom.: 49 Cov.: 32 AF XY: 0.0175 AC XY: 1298 AN XY: 74374

Gnomad4 AFR AF: 0.00494

Gnomad4 AMR AF: 0.0148

Gnomad4 ASJ AF: 0.0421

Gnomad4 EAS AF: 0.00675

Gnomad4 SAS AF: 0.0364

Gnomad4 FIN AF: 0.00887

Gnomad4 NFE AF: 0.0255

Gnomad4 OTH AF: 0.0232

Alfa AF: 0.0263 Hom.: 164

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	-0.49
CADD	Benign	4.1
DANN	Benign	0.47

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: rs4986990; hg19: chr8-18080015;