8-18223238-T-G

Position:

• chr8-18223238-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000662.8(NAT1):​c.*318T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.651 in 168,204 control chromosomes in the GnomAD database, including 36,695 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 0.64 (32583 hom., cov: 32)
  • Exomes 𝑓: 0.71 (4112 hom.)
• Consequence: NAT1 NM_000662.8 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0120

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.739 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NAT1	NM_000662.8	c.*318T>G		3_prime_UTR_variant	3/3	ENST00000307719.9	NP_000653.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NAT1	ENST00000307719.9	c.*318T>G		3_prime_UTR_variant	3/3	1	NM_000662.8	ENSP00000307218.4

Frequencies

GnomAD3 genomes AF: 0.645 AC: 97890 AN: 151762 Hom.: 32564 Cov.: 32

Gnomad AFR AF: 0.492

Gnomad AMI AF: 0.726

Gnomad AMR AF: 0.626

Gnomad ASJ AF: 0.722

Gnomad EAS AF: 0.471

Gnomad SAS AF: 0.599

Gnomad FIN AF: 0.703

Gnomad MID AF: 0.624

Gnomad NFE AF: 0.744

Gnomad OTH AF: 0.651

GnomAD4 exome AF: 0.708 AC: 11564 AN: 16326 Hom.: 4112 Cov.: 0 AF XY: 0.705 AC XY: 5487 AN XY: 7780

Gnomad4 AFR exome AF: 0.480

Gnomad4 AMR exome AF: 0.740

Gnomad4 ASJ exome AF: 0.656

Gnomad4 EAS exome AF: 0.568

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.708

Gnomad4 NFE exome AF: 0.738

Gnomad4 OTH exome AF: 0.725

GnomAD4 genome AF: 0.645 AC: 97947 AN: 151878 Hom.: 32583 Cov.: 32 AF XY: 0.641 AC XY: 47544 AN XY: 74222

Gnomad4 AFR AF: 0.492

Gnomad4 AMR AF: 0.626

Gnomad4 ASJ AF: 0.722

Gnomad4 EAS AF: 0.471

Gnomad4 SAS AF: 0.599

Gnomad4 FIN AF: 0.703

Gnomad4 NFE AF: 0.744

Gnomad4 OTH AF: 0.646

Alfa AF: 0.722 Hom.: 65216

Bravo AF: 0.633

Asia WGS AF: 0.530 AC: 1831 AN: 3456

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.9
DANN	Benign	0.83

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: rs4986993; hg19: chr8-18080747; COSMIC: COSV56986474; COSMIC: COSV56986474;