rs7845127

Variant names:

• chr8-18209886-T-C
• rs7845127
• ENST00000517441.5:n.198T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000517441.5(NAT1):​n.198T>C variant causes a non coding transcript exon 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 ENST00000517441.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.00
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
NAT1	NM_000662.8	c.-380T>C		upstream_gene_variant		ENST00000307719.9	NP_000653.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAT1	ENST00000517441.5	n.198T>C		non_coding_transcript_exon_variant	Exon 3 of 5	2
NAT1	ENST00000307719.9	c.-380T>C		upstream_gene_variant		1	NM_000662.8	ENSP00000307218.4
NAT1	ENST00000518029.5	c.-764T>C		upstream_gene_variant		1		ENSP00000428270.1
NAT1	ENST00000517574.5	n.-248T>C		upstream_gene_variant		3

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.917 AC: 22 AN: 24

Other (OTH) AF: 1.00 AC: 4 AN: 4

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

African (AFR) AF: 0.914 AC: 37938 AN: 41494

American (AMR) AF: 0.687 AC: 10502 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.731 AC: 2538 AN: 3472

East Asian (EAS) AF: 0.619 AC: 3182 AN: 5144

South Asian (SAS) AF: 0.660 AC: 3172 AN: 4808

European-Finnish (FIN) AF: 0.716 AC: 7555 AN: 10556

Middle Eastern (MID) AF: 0.796 AC: 234 AN: 294

European-Non Finnish (NFE) AF: 0.701 AC: 47625 AN: 67960

Other (OTH) AF: 0.740 AC: 1563 AN: 2112

Alfa AF: 0.725 Hom.: 100948

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
PhyloP100		-2.0
PromoterAI		-0.035	Neutral
Mutation Taster		=298/2	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs7845127; hg19: chr8-18067395;