8-18221342-A-G

Variant names:

• chr8-18221342-A-G
• rs8190851
• NM_000662.8:c.-6-700A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000662.8(NAT1):​c.-6-700A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0179 in 148,106 control chromosomes in the GnomAD database, including 48 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 0.018 (48 hom., cov: 31)
• Consequence: NAT1 NM_000662.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.440
• Publications: 1 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=-0.97).
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0179 (2649/148106) while in subpopulation SAS AF = 0.0361 (169/4678). AF 95% confidence interval is 0.0317. There are 48 homozygotes in GnomAd4. There are 1230 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2649 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000662.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAT1	NM_000662.8	MANE Select	c.-6-700A>G		intron	N/A	NP_000653.3
	NAT1	NM_001160175.4		c.181-700A>G		intron	N/A	NP_001153647.1
	NAT1	NM_001160176.4		c.181-700A>G		intron	N/A	NP_001153648.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAT1	ENST00000307719.9	TSL:1 MANE Select	c.-6-700A>G		intron	N/A	ENSP00000307218.4
	NAT1	ENST00000518029.5	TSL:1	c.-6-700A>G		intron	N/A	ENSP00000428270.1
	NAT1	ENST00000519006.5	TSL:1	n.522-700A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0179 AC: 2642 AN: 148006 Hom.: 48 Cov.: 31

Gnomad AFR AF: 0.00453

Gnomad AMI AF: 0.0815

Gnomad AMR AF: 0.0145

Gnomad ASJ AF: 0.0417

Gnomad EAS AF: 0.00594

Gnomad SAS AF: 0.0356

Gnomad FIN AF: 0.00783

Gnomad MID AF: 0.0796

Gnomad NFE AF: 0.0251

Gnomad OTH AF: 0.0221

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

GnomAD4 genome AF: 0.0179 AC: 2649 AN: 148106 Hom.: 48 Cov.: 31 AF XY: 0.0171 AC XY: 1230 AN XY: 71974

African (AFR) AF: 0.00456 AC: 184 AN: 40328

American (AMR) AF: 0.0145 AC: 215 AN: 14850

Ashkenazi Jewish (ASJ) AF: 0.0417 AC: 144 AN: 3450

East Asian (EAS) AF: 0.00596 AC: 30 AN: 5036

South Asian (SAS) AF: 0.0361 AC: 169 AN: 4678

European-Finnish (FIN) AF: 0.00783 AC: 74 AN: 9450

Middle Eastern (MID) AF: 0.0856 AC: 25 AN: 292

European-Non Finnish (NFE) AF: 0.0252 AC: 1688 AN: 67052

Other (OTH) AF: 0.0223 AC: 46 AN: 2062

Alfa AF: 0.0247 Hom.: 87

Bravo AF: 0.0174

Asia WGS AF: 0.0180 AC: 63 AN: 3456

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	5.1
DANN	Benign	0.58
PhyloP100		-0.44
PromoterAI		-0.0073	Neutral
Mutation Taster		=100/0	polymorphism

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: rs8190851; hg19: chr8-18078851;