chr8-18221704-C-T

Position:

• chr8-18221704-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000307719.9(NAT1):​c.-6-338C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0191 in 209,604 control chromosomes in the GnomAD database, including 63 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 (49 hom., cov: 32)
  • Exomes 𝑓: 0.022 (14 hom.)
• Consequence: NAT1 ENST00000307719.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.681

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=-1.0).
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0181 (2760/152158) while in subpopulation SAS AF= 0.0361 (174/4820). AF 95% confidence interval is 0.0317. There are 49 homozygotes in gnomad4. There are 1295 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2760 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NAT1	NM_000662.8	c.-6-338C>T		intron_variant		ENST00000307719.9	NP_000653.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NAT1	ENST00000307719.9	c.-6-338C>T		intron_variant		1	NM_000662.8	ENSP00000307218	P1

Frequencies

GnomAD3 genomes AF: 0.0181 AC: 2752 AN: 152040 Hom.: 49 Cov.: 32

Gnomad AFR AF: 0.00488

Gnomad AMI AF: 0.0802

Gnomad AMR AF: 0.0147

Gnomad ASJ AF: 0.0421

Gnomad EAS AF: 0.00638

Gnomad SAS AF: 0.0354

Gnomad FIN AF: 0.00877

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0255

Gnomad OTH AF: 0.0229

GnomAD4 exome AF: 0.0217 AC: 1244 AN: 57446 Hom.: 14 AF XY: 0.0229 AC XY: 687 AN XY: 30052

Gnomad4 AFR exome AF: 0.00467

Gnomad4 AMR exome AF: 0.0154

Gnomad4 ASJ exome AF: 0.0411

Gnomad4 EAS exome AF: 0.00715

Gnomad4 SAS exome AF: 0.0247

Gnomad4 FIN exome AF: 0.0105

Gnomad4 NFE exome AF: 0.0229

Gnomad4 OTH exome AF: 0.0228

GnomAD4 genome AF: 0.0181 AC: 2760 AN: 152158 Hom.: 49 Cov.: 32 AF XY: 0.0174 AC XY: 1295 AN XY: 74384

Gnomad4 AFR AF: 0.00491

Gnomad4 AMR AF: 0.0147

Gnomad4 ASJ AF: 0.0421

Gnomad4 EAS AF: 0.00639

Gnomad4 SAS AF: 0.0361

Gnomad4 FIN AF: 0.00877

Gnomad4 NFE AF: 0.0256

Gnomad4 OTH AF: 0.0232

Alfa AF: 0.0236 Hom.: 68

Bravo AF: 0.0174

Asia WGS AF: 0.0240 AC: 83 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.0
DANN	Benign	0.52

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: rs4986988; hg19: chr8-18079213;