chr8-18194154-G-A

Variant names:

• chr8-18194154-G-A
• rs11778588
• NM_001291962.2:c.-192-15627G>A

Variant summary

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

The NM_001291962.2(NAT1):​c.-192-15627G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0554 in 152,200 control chromosomes in the GnomAD database, including 313 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 0.055 (313 hom., cov: 31)
• Consequence: NAT1 NM_001291962.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.164
• Publications: 2 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0871 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAT1	NM_001291962.2		c.-192-15627G>A		intron	N/A	NP_001278891.1
	NAT1	NM_001160179.3		c.-260-15627G>A		intron	N/A	NP_001153651.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAT1	ENST00000903000.1		c.-378-15627G>A		intron	N/A	ENSP00000573059.1
	NAT1	ENST00000903001.1		c.-591-11875G>A		intron	N/A	ENSP00000573060.1
	NAT1	ENST00000903002.1		c.-306-8290G>A		intron	N/A	ENSP00000573061.1

Frequencies

GnomAD3 genomes AF: 0.0555 AC: 8433 AN: 152082 Hom.: 313 Cov.: 31

Gnomad AFR AF: 0.0171

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.0476

Gnomad ASJ AF: 0.0429

Gnomad EAS AF: 0.000966

Gnomad SAS AF: 0.0240

Gnomad FIN AF: 0.0538

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0890

Gnomad OTH AF: 0.0407

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

GnomAD4 genome AF: 0.0554 AC: 8430 AN: 152200 Hom.: 313 Cov.: 31 AF XY: 0.0527 AC XY: 3920 AN XY: 74400

African (AFR) AF: 0.0170 AC: 707 AN: 41550

American (AMR) AF: 0.0474 AC: 725 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0429 AC: 149 AN: 3470

East Asian (EAS) AF: 0.000969 AC: 5 AN: 5162

South Asian (SAS) AF: 0.0240 AC: 116 AN: 4824

European-Finnish (FIN) AF: 0.0538 AC: 571 AN: 10606

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0890 AC: 6049 AN: 67990

Other (OTH) AF: 0.0398 AC: 84 AN: 2112

Alfa AF: 0.0797 Hom.: 251

Bravo AF: 0.0534

Asia WGS AF: 0.0120 AC: 42 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.6
DANN	Benign	0.86
PhyloP100		0.16
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: rs11778588; hg19: chr8-18051663;