rs8190851

Positions:

• chr8-18221342-A-G
• chr8-18221342-A-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.97).
• 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 male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2649 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NAT1	NM_000662.8	c.-6-700A>G		intron_variant		ENST00000307719.9	NP_000653.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NAT1	ENST00000307719.9	c.-6-700A>G		intron_variant		1	NM_000662.8	ENSP00000307218	P1

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

Gnomad4 AFR AF: 0.00456

Gnomad4 AMR AF: 0.0145

Gnomad4 ASJ AF: 0.0417

Gnomad4 EAS AF: 0.00596

Gnomad4 SAS AF: 0.0361

Gnomad4 FIN AF: 0.00783

Gnomad4 NFE AF: 0.0252

Gnomad4 OTH AF: 0.0223

Alfa AF: 0.0261 Hom.: 73

Bravo AF: 0.0174

Asia WGS AF: 0.0180 AC: 63 AN: 3456

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	5.1
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: rs8190851; hg19: chr8-18078851;