rs9325827

Variant names:

• chr8-18215673-T-C
• rs9325827
• NM_000662.8:c.-85-3738T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 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=-0.92).
• 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 rank	MANE	Protein	UniProt
NAT1	NM_000662.8	c.-85-3738T>C		intron_variant	Intron 1 of 2	ENST00000307719.9	NP_000653.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAT1	ENST00000307719.9	c.-85-3738T>C		intron_variant	Intron 1 of 2	1	NM_000662.8	ENSP00000307218.4

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

African (AFR) AF: 0.0661 AC: 2744 AN: 41536

American (AMR) AF: 0.199 AC: 3046 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 548 AN: 3472

East Asian (EAS) AF: 0.365 AC: 1883 AN: 5154

South Asian (SAS) AF: 0.241 AC: 1159 AN: 4814

European-Finnish (FIN) AF: 0.120 AC: 1266 AN: 10586

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.150 AC: 10179 AN: 68004

Other (OTH) AF: 0.152 AC: 322 AN: 2114

Alfa AF: 0.153 Hom.: 2498

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
PhyloP100		-0.21
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9325827; hg19: chr8-18073182;