rs11778588

chr8-18194154-G-A

Variant summary

Our verdict is Benign. Variant got -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

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0871 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NAT1	NM_001160179.3	c.-260-15627G>A		intron_variant
NAT1	NM_001291962.2	c.-192-15627G>A		intron_variant
NAT1	XM_047422397.1	c.-815-15627G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAT1	ENST00000517441.5	n.93-15627G>A		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 AFR AF: 0.0170

Gnomad4 AMR AF: 0.0474

Gnomad4 ASJ AF: 0.0429

Gnomad4 EAS AF: 0.000969

Gnomad4 SAS AF: 0.0240

Gnomad4 FIN AF: 0.0538

Gnomad4 NFE AF: 0.0890

Gnomad4 OTH AF: 0.0398

Alfa AF: 0.0761 Hom.: 132

Bravo AF: 0.0534

Asia WGS AF: 0.0120 AC: 42 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	1.6
Dann	Benign	0.86

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11778588; hg19: chr8-18051663;