rs4921580

chr8-18213491-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000662.8(NAT1):c.-86+3311C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 151,984 control chromosomes in the GnomAD database, including 1,791 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 0.15 (1791 hom., cov: 30)
• Consequence: NAT1 NM_000662.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.134

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NAT1	NM_000662.8	c.-86+3311C>G		intron_variant		ENST00000307719.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAT1	ENST00000307719.9	c.-86+3311C>G		intron_variant		1	NM_000662.8	P1

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22770 AN: 151866 Hom.: 1786 Cov.: 30

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.0758

Gnomad AMR AF: 0.145

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.186

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.157

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

GnomAD4 genome AF: 0.150 AC: 22792 AN: 151984 Hom.: 1791 Cov.: 30 AF XY: 0.152 AC XY: 11296 AN XY: 74292

Gnomad4 AFR AF: 0.185

Gnomad4 AMR AF: 0.145

Gnomad4 ASJ AF: 0.131

Gnomad4 EAS AF: 0.185

Gnomad4 SAS AF: 0.137

Gnomad4 FIN AF: 0.152

Gnomad4 NFE AF: 0.129

Gnomad4 OTH AF: 0.159

Alfa AF: 0.144 Hom.: 196

Bravo AF: 0.153

Asia WGS AF: 0.151 AC: 525 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.69
Dann	Benign	0.58

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: rs4921580; hg19: chr8-18071000;