rs4986990

Variant names:

• chr8-18222506-G-A
• rs4986990
• NM_000662.8:c.459G>A

Variant summary

Our verdict is Benign. The variant received -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. Variant has been reported in ClinVar as (no stars). Synonymous variant affecting the same amino acid position (i.e. T153T) has been classified as Uncertain significance.

• 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
• Publications: 27 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000662.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAT1	NM_000662.8	MANE Select	c.459G>A	p.Thr153Thr	synonymous	Exon 3 of 3	NP_000653.3
	NAT1	NM_001160175.4		c.645G>A	p.Thr215Thr	synonymous	Exon 5 of 5	NP_001153647.1	F5H5R8
	NAT1	NM_001160176.4		c.645G>A	p.Thr215Thr	synonymous	Exon 4 of 4	NP_001153648.1	F5H5R8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAT1	ENST00000307719.9	TSL:1 MANE Select	c.459G>A	p.Thr153Thr	synonymous	Exon 3 of 3	ENSP00000307218.4	P18440
	NAT1	ENST00000518029.5	TSL:1	c.459G>A	p.Thr153Thr	synonymous	Exon 4 of 4	ENSP00000428270.1	P18440
	NAT1	ENST00000545197.3	TSL:5	c.645G>A	p.Thr215Thr	synonymous	Exon 4 of 4	ENSP00000443194.1	F5H5R8

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

GnomAD2 exomes AF: 0.0203 AC: 5107 AN: 251132 AF XY: 0.0217

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 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

African (AFR) AF: 0.00505 AC: 169 AN: 33472

American (AMR) AF: 0.0115 AC: 516 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.0445 AC: 1164 AN: 26132

East Asian (EAS) AF: 0.00587 AC: 233 AN: 39698

South Asian (SAS) AF: 0.0270 AC: 2327 AN: 86256

European-Finnish (FIN) AF: 0.00957 AC: 511 AN: 53416

Middle Eastern (MID) AF: 0.0801 AC: 462 AN: 5768

European-Non Finnish (NFE) AF: 0.0224 AC: 24912 AN: 1111976

Other (OTH) AF: 0.0270 AC: 1631 AN: 60394

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

African (AFR) AF: 0.00494 AC: 205 AN: 41492

American (AMR) AF: 0.0148 AC: 226 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0421 AC: 146 AN: 3468

East Asian (EAS) AF: 0.00675 AC: 35 AN: 5184

South Asian (SAS) AF: 0.0364 AC: 175 AN: 4814

European-Finnish (FIN) AF: 0.00887 AC: 94 AN: 10596

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0255 AC: 1736 AN: 67996

Other (OTH) AF: 0.0232 AC: 49 AN: 2114

Alfa AF: 0.0246 Hom.: 277

Bravo AF: 0.0174

Asia WGS AF: 0.0240 AC: 83 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	4.1
DANN	Benign	0.47
PhyloP100		-0.75
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4986990; hg19: chr8-18080015; COSMIC: COSV107329185; COSMIC: COSV107329185;