8-18223135-A-T

Position:

• chr8-18223135-A-T

Variant summary

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

The ENST00000307719.9(NAT1):​c.*215A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.673 in 149,482 control chromosomes in the GnomAD database, including 34,413 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 0.67 (34413 hom., cov: 31)
  • Exomes 𝑓: 0.69 (11308 hom.)
  • Failed GnomAD Quality Control
• Consequence: NAT1 ENST00000307719.9 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00

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=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.77 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NAT1	NM_000662.8	c.*215A>T		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.*215A>T		3_prime_UTR_variant	3/3	1	NM_000662.8	ENSP00000307218	P1

Frequencies

GnomAD3 genomes AF: 0.673 AC: 100474 AN: 149370 Hom.: 34395 Cov.: 31

Gnomad AFR AF: 0.522

Gnomad AMI AF: 0.759

Gnomad AMR AF: 0.641

Gnomad ASJ AF: 0.741

Gnomad EAS AF: 0.486

Gnomad SAS AF: 0.625

Gnomad FIN AF: 0.733

Gnomad MID AF: 0.662

Gnomad NFE AF: 0.776

Gnomad OTH AF: 0.676

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.693 AC: 34417 AN: 49684 Hom.: 11308 Cov.: 3 AF XY: 0.696 AC XY: 17632 AN XY: 25322

Gnomad4 AFR exome AF: 0.501

Gnomad4 AMR exome AF: 0.609

Gnomad4 ASJ exome AF: 0.721

Gnomad4 EAS exome AF: 0.492

Gnomad4 SAS exome AF: 0.569

Gnomad4 FIN exome AF: 0.674

Gnomad4 NFE exome AF: 0.742

Gnomad4 OTH exome AF: 0.687

GnomAD4 genome AF: 0.673 AC: 100528 AN: 149482 Hom.: 34413 Cov.: 31 AF XY: 0.667 AC XY: 48760 AN XY: 73092

Gnomad4 AFR AF: 0.522

Gnomad4 AMR AF: 0.641

Gnomad4 ASJ AF: 0.741

Gnomad4 EAS AF: 0.486

Gnomad4 SAS AF: 0.626

Gnomad4 FIN AF: 0.733

Gnomad4 NFE AF: 0.776

Gnomad4 OTH AF: 0.670

Alfa AF: 0.702 Hom.: 3626

Bravo AF: 0.658

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.4
DANN	Benign	0.34

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: rs1057126; hg19: chr8-18080644; COSMIC: COSV56986088; COSMIC: COSV56986088;