rs4921877

Variant names:

• chr8-18198075-T-A
• rs4921877
• NM_001291962.2:c.-192-11706T>A

Your query was ambiguous. Multiple possible variants found:

• chr8-18198075-T-A
• chr8-18198075-T-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001291962.2(NAT1):​c.-192-11706T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.766 in 152,006 control chromosomes in the GnomAD database, including 44,986 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 0.77 (44986 hom., cov: 30)
• Consequence: NAT1 NM_001291962.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.494
• Publications: 4 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.859 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001291962.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAT1	NM_001291962.2		c.-192-11706T>A		intron	N/A	NP_001278891.1
	NAT1	NM_001160179.3		c.-260-11706T>A		intron	N/A	NP_001153651.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAT1	ENST00000517441.5	TSL:2	n.93-11706T>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.766 AC: 116306 AN: 151888 Hom.: 44944 Cov.: 30

Gnomad AFR AF: 0.867

Gnomad AMI AF: 0.603

Gnomad AMR AF: 0.720

Gnomad ASJ AF: 0.724

Gnomad EAS AF: 0.592

Gnomad SAS AF: 0.639

Gnomad FIN AF: 0.760

Gnomad MID AF: 0.820

Gnomad NFE AF: 0.741

Gnomad OTH AF: 0.772

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

GnomAD4 genome AF: 0.766 AC: 116401 AN: 152006 Hom.: 44986 Cov.: 30 AF XY: 0.761 AC XY: 56564 AN XY: 74302

African (AFR) AF: 0.867 AC: 35971 AN: 41490

American (AMR) AF: 0.721 AC: 10989 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.724 AC: 2515 AN: 3472

East Asian (EAS) AF: 0.592 AC: 3058 AN: 5168

South Asian (SAS) AF: 0.640 AC: 3084 AN: 4822

European-Finnish (FIN) AF: 0.760 AC: 8030 AN: 10562

Middle Eastern (MID) AF: 0.830 AC: 244 AN: 294

European-Non Finnish (NFE) AF: 0.741 AC: 50339 AN: 67934

Other (OTH) AF: 0.770 AC: 1625 AN: 2110

Alfa AF: 0.753 Hom.: 5388

Bravo AF: 0.767

Asia WGS AF: 0.635 AC: 2209 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.6
DANN	Benign	0.63
PhyloP100		-0.49
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs4921877; hg19: chr8-18055584;