rs7845127

Positions:

• chr8-18209886-T-C

Variant summary

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

The NM_001291962.2(NAT1):​c.-87T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.756 in 152,064 control chromosomes in the GnomAD database, including 44,237 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 0.76 (44225 hom., cov: 30)
  • Exomes 𝑓: 0.93 (12 hom.)
• Consequence: NAT1 NM_001291962.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.00

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]

NAT1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.907 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NAT1	NM_001291962.2	c.-87T>C		5_prime_UTR_variant	3/6		NP_001278891.1
NAT1	NM_001160179.3	c.-155T>C		5_prime_UTR_variant	3/5		NP_001153651.1
NAT1	XM_047422397.1	c.-710T>C		5_prime_UTR_variant	3/9		XP_047278353.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NAT1	ENST00000517441.5	n.198T>C		non_coding_transcript_exon_variant	3/5	2

Frequencies

GnomAD3 genomes AF: 0.756 AC: 114832 AN: 151918 Hom.: 44160 Cov.: 30

Gnomad AFR AF: 0.914

Gnomad AMI AF: 0.712

Gnomad AMR AF: 0.687

Gnomad ASJ AF: 0.731

Gnomad EAS AF: 0.619

Gnomad SAS AF: 0.659

Gnomad FIN AF: 0.716

Gnomad MID AF: 0.794

Gnomad NFE AF: 0.701

Gnomad OTH AF: 0.740

GnomAD4 exome AF: 0.929 AC: 26 AN: 28 Hom.: 12 Cov.: 0 AF XY: 0.917 AC XY: 22 AN XY: 24

Gnomad4 NFE exome AF: 0.917

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.756 AC: 114957 AN: 152036 Hom.: 44225 Cov.: 30 AF XY: 0.752 AC XY: 55855 AN XY: 74302

Gnomad4 AFR AF: 0.914

Gnomad4 AMR AF: 0.687

Gnomad4 ASJ AF: 0.731

Gnomad4 EAS AF: 0.619

Gnomad4 SAS AF: 0.660

Gnomad4 FIN AF: 0.716

Gnomad4 NFE AF: 0.701

Gnomad4 OTH AF: 0.740

Alfa AF: 0.710 Hom.: 64224

Bravo AF: 0.760

Asia WGS AF: 0.661 AC: 2299 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.5
DANN	Benign	0.60

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7845127; hg19: chr8-18067395;