8-18221704-C-T

Variant names:

• chr8-18221704-C-T
• rs4986988
• NM_000662.8:c.-6-338C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001160174.3(NAT1):​c.-344C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0191 in 209,604 control chromosomes in the GnomAD database, including 63 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 0.018 (49 hom., cov: 32)
  • Exomes 𝑓: 0.022 (14 hom.)
• Consequence: NAT1 NM_001160174.3 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.681
• Publications: 15 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=-1.0).
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0181 (2760/152158) while in subpopulation SAS AF = 0.0361 (174/4820). AF 95% confidence interval is 0.0317. There are 49 homozygotes in GnomAd4. There are 1295 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2760 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001160174.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAT1	NM_000662.8	MANE Select	c.-6-338C>T		intron	N/A	NP_000653.3
	NAT1	NM_001160174.3		c.-344C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 1	NP_001153646.1	P18440
	NAT1	NM_001160174.3		c.-344C>T		5_prime_UTR	Exon 1 of 1	NP_001153646.1	P18440

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAT1	ENST00000307719.9	TSL:1 MANE Select	c.-6-338C>T		intron	N/A	ENSP00000307218.4	P18440
	NAT1	ENST00000518029.5	TSL:1	c.-6-338C>T		intron	N/A	ENSP00000428270.1	P18440
	NAT1	ENST00000519006.5	TSL:1	n.522-338C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0181 AC: 2752 AN: 152040 Hom.: 49 Cov.: 32

Gnomad AFR AF: 0.00488

Gnomad AMI AF: 0.0802

Gnomad AMR AF: 0.0147

Gnomad ASJ AF: 0.0421

Gnomad EAS AF: 0.00638

Gnomad SAS AF: 0.0354

Gnomad FIN AF: 0.00877

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0255

Gnomad OTH AF: 0.0229

GnomAD4 exome AF: 0.0217 AC: 1244 AN: 57446 Hom.: 14 AF XY: 0.0229 AC XY: 687 AN XY: 30052

African (AFR) AF: 0.00467 AC: 5 AN: 1070

American (AMR) AF: 0.0154 AC: 53 AN: 3452

Ashkenazi Jewish (ASJ) AF: 0.0411 AC: 62 AN: 1510

East Asian (EAS) AF: 0.00715 AC: 20 AN: 2796

South Asian (SAS) AF: 0.0247 AC: 153 AN: 6186

European-Finnish (FIN) AF: 0.0105 AC: 26 AN: 2468

Middle Eastern (MID) AF: 0.0686 AC: 14 AN: 204

European-Non Finnish (NFE) AF: 0.0229 AC: 840 AN: 36652

Other (OTH) AF: 0.0228 AC: 71 AN: 3108

GnomAD4 genome AF: 0.0181 AC: 2760 AN: 152158 Hom.: 49 Cov.: 32 AF XY: 0.0174 AC XY: 1295 AN XY: 74384

African (AFR) AF: 0.00491 AC: 204 AN: 41508

American (AMR) AF: 0.0147 AC: 225 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0421 AC: 146 AN: 3470

East Asian (EAS) AF: 0.00639 AC: 33 AN: 5162

South Asian (SAS) AF: 0.0361 AC: 174 AN: 4820

European-Finnish (FIN) AF: 0.00877 AC: 93 AN: 10602

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0256 AC: 1738 AN: 67996

Other (OTH) AF: 0.0232 AC: 49 AN: 2114

Alfa AF: 0.0237 Hom.: 149

Bravo AF: 0.0174

Asia WGS AF: 0.0240 AC: 83 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.0
DANN	Benign	0.52
PhyloP100		-0.68
PromoterAI		0.0081	Neutral
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs4986988; hg19: chr8-18079213;