chr8-18211326-T-C

Position:

• chr8-18211326-T-C

Variant summary

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

The NM_001160175.4(NAT1):​c.-34T>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 0.726 in 152,182 control chromosomes in the GnomAD database, including 40,829 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 0.73 (40816 hom., cov: 31)
  • Exomes 𝑓: 0.65 (13 hom.)
• Consequence: NAT1 NM_001160175.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.92

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.88 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NAT1	NM_000662.8	c.-86+1146T>C		intron_variant		ENST00000307719.9	NP_000653.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NAT1	ENST00000307719.9	c.-86+1146T>C		intron_variant		1	NM_000662.8	ENSP00000307218.4

Frequencies

GnomAD3 genomes AF: 0.725 AC: 110258 AN: 152004 Hom.: 40758 Cov.: 31

Gnomad AFR AF: 0.888

Gnomad AMI AF: 0.545

Gnomad AMR AF: 0.661

Gnomad ASJ AF: 0.674

Gnomad EAS AF: 0.623

Gnomad SAS AF: 0.626

Gnomad FIN AF: 0.708

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.664

Gnomad OTH AF: 0.711

GnomAD4 exome AF: 0.650 AC: 39 AN: 60 Hom.: 13 Cov.: 0 AF XY: 0.660 AC XY: 33 AN XY: 50

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.635

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.726 AC: 110376 AN: 152122 Hom.: 40816 Cov.: 31 AF XY: 0.722 AC XY: 53694 AN XY: 74350

Gnomad4 AFR AF: 0.888

Gnomad4 AMR AF: 0.661

Gnomad4 ASJ AF: 0.674

Gnomad4 EAS AF: 0.622

Gnomad4 SAS AF: 0.627

Gnomad4 FIN AF: 0.708

Gnomad4 NFE AF: 0.664

Gnomad4 OTH AF: 0.712

Alfa AF: 0.675 Hom.: 60212

Bravo AF: 0.729

Asia WGS AF: 0.650 AC: 2262 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.058
DANN	Benign	0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs2410545; hg19: chr8-18068835;