rs8190842

chr8-18220936-G-Achr8-18220936-G-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.-6-1106G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0259 in 152,184 control chromosomes in the GnomAD database, including 74 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 0.026 (74 hom., cov: 32)
• Consequence: NAT1 NM_000662.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.387

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=-0.91).
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0259 (3943/152184) while in subpopulation SAS AF= 0.0367 (177/4826). AF 95% confidence interval is 0.0323. There are 74 homozygotes in gnomad4. There are 1863 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd at 3931 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NAT1	NM_000662.8	c.-6-1106G>A		intron_variant		ENST00000307719.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAT1	ENST00000307719.9	c.-6-1106G>A		intron_variant		1	NM_000662.8	P1

Frequencies

GnomAD3 genomes AF: 0.0259 AC: 3931 AN: 152066 Hom.: 74 Cov.: 32

Gnomad AFR AF: 0.0318

Gnomad AMI AF: 0.0813

Gnomad AMR AF: 0.0172

Gnomad ASJ AF: 0.0418

Gnomad EAS AF: 0.00656

Gnomad SAS AF: 0.0360

Gnomad FIN AF: 0.00878

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0257

Gnomad OTH AF: 0.0282

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

GnomAD4 genome AF: 0.0259 AC: 3943 AN: 152184 Hom.: 74 Cov.: 32 AF XY: 0.0250 AC XY: 1863 AN XY: 74400

Gnomad4 AFR AF: 0.0318

Gnomad4 AMR AF: 0.0172

Gnomad4 ASJ AF: 0.0418

Gnomad4 EAS AF: 0.00658

Gnomad4 SAS AF: 0.0367

Gnomad4 FIN AF: 0.00878

Gnomad4 NFE AF: 0.0257

Gnomad4 OTH AF: 0.0284

Alfa AF: 0.0262 Hom.: 77

Bravo AF: 0.0265

Asia WGS AF: 0.0260 AC: 91 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	4.8
Dann	Benign	0.70

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: rs8190842; hg19: chr8-18078445;