rs15561

chr8-18223142-A-Cchr8-18223142-A-T

Variant summary

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

The NM_000662.8(NAT1):c.*222A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.644 in 151,056 control chromosomes in the GnomAD database, including 32,271 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 (32271 hom., cov: 31)
  • Exomes 𝑓: 0.71 (11891 hom.)
  • Failed GnomAD Quality Control
• Consequence: NAT1 NM_000662.8 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.738 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NAT1	NM_000662.8	c.*222A>C		3_prime_UTR_variant	3/3	ENST00000307719.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAT1	ENST00000307719.9	c.*222A>C		3_prime_UTR_variant	3/3	1	NM_000662.8	P1

Frequencies

GnomAD3 genomes AF: 0.644 AC: 97181 AN: 150942 Hom.: 32252 Cov.: 31

Gnomad AFR AF: 0.491

Gnomad AMI AF: 0.724

Gnomad AMR AF: 0.624

Gnomad ASJ AF: 0.721

Gnomad EAS AF: 0.471

Gnomad SAS AF: 0.599

Gnomad FIN AF: 0.701

Gnomad MID AF: 0.619

Gnomad NFE AF: 0.744

Gnomad OTH AF: 0.651

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.707 AC: 33425 AN: 47294 Hom.: 11891 Cov.: 3 AF XY: 0.709 AC XY: 17065 AN XY: 24064

Gnomad4 AFR exome AF: 0.499

Gnomad4 AMR exome AF: 0.636

Gnomad4 ASJ exome AF: 0.701

Gnomad4 EAS exome AF: 0.502

Gnomad4 SAS exome AF: 0.563

Gnomad4 FIN exome AF: 0.707

Gnomad4 NFE exome AF: 0.747

Gnomad4 OTH exome AF: 0.690

GnomAD4 genome AF: 0.644 AC: 97238 AN: 151056 Hom.: 32271 Cov.: 31 AF XY: 0.639 AC XY: 47191 AN XY: 73800

Gnomad4 AFR AF: 0.491

Gnomad4 AMR AF: 0.624

Gnomad4 ASJ AF: 0.721

Gnomad4 EAS AF: 0.471

Gnomad4 SAS AF: 0.599

Gnomad4 FIN AF: 0.701

Gnomad4 NFE AF: 0.744

Gnomad4 OTH AF: 0.646

Alfa AF: 0.718 Hom.: 66967

Bravo AF: 0.633

Asia WGS AF: 0.529 AC: 1813 AN: 3426

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.42
Dann	Benign	0.64

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: rs15561; hg19: chr8-18080651; COSMIC: COSV56986098; COSMIC: COSV56986098;