rs9325827

chr8-18215673-T-C

Variant summary

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

The NM_000662.8(NAT1):c.-85-3738T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 152,170 control chromosomes in the GnomAD database, including 1,810 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 0.14 (1810 hom., cov: 33)
• Consequence: NAT1 NM_000662.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.210

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.352 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NAT1	NM_000662.8	c.-85-3738T>C		intron_variant		ENST00000307719.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAT1	ENST00000307719.9	c.-85-3738T>C		intron_variant		1	NM_000662.8	P1

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21310 AN: 152052 Hom.: 1806 Cov.: 33

Gnomad AFR AF: 0.0661

Gnomad AMI AF: 0.132

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.364

Gnomad SAS AF: 0.240

Gnomad FIN AF: 0.120

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.152

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

GnomAD4 genome AF: 0.140 AC: 21319 AN: 152170 Hom.: 1810 Cov.: 33 AF XY: 0.143 AC XY: 10673 AN XY: 74392

Gnomad4 AFR AF: 0.0661

Gnomad4 AMR AF: 0.199

Gnomad4 ASJ AF: 0.158

Gnomad4 EAS AF: 0.365

Gnomad4 SAS AF: 0.241

Gnomad4 FIN AF: 0.120

Gnomad4 NFE AF: 0.150

Gnomad4 OTH AF: 0.152

Alfa AF: 0.156 Hom.: 1883

Bravo AF: 0.143

Asia WGS AF: 0.275 AC: 954 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	1.5
Dann	Benign	0.44

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: rs9325827; hg19: chr8-18073182;