rs8190866

Variant names:

• chr8-18223693-CT-C
• rs8190866
• NM_000662.8:c.*774delT

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_000662.8(NAT1):​c.*774delT variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.063 (390 hom., cov: 31)
  • Exomes 𝑓: 0.098 (22 hom.)
  • Failed GnomAD Quality Control
• Consequence: NAT1 NM_000662.8 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.717
• Publications: 0 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 883 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAT1	NM_000662.8	c.*774delT		downstream_gene_variant		ENST00000307719.9	NP_000653.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAT1	ENST00000307719.9	c.*774delT		downstream_gene_variant		1	NM_000662.8	ENSP00000307218.4
NAT1	ENST00000518029.5	c.*774delT		downstream_gene_variant		1		ENSP00000428270.1
NAT1	ENST00000545197.3	c.*774delT		downstream_gene_variant		5		ENSP00000443194.1
NAT1	ENST00000517492.5	c.*774delT		downstream_gene_variant		2		ENSP00000429407.1

Frequencies

GnomAD3 genomes AF: 0.0636 AC: 9559 AN: 150336 Hom.: 392 Cov.: 31

Gnomad AFR AF: 0.0201

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.0508

Gnomad ASJ AF: 0.0950

Gnomad EAS AF: 0.0122

Gnomad SAS AF: 0.0938

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0820

Gnomad OTH AF: 0.0572

GnomAD4 exome AF: 0.0975 AC: 883 AN: 9052 Hom.: 22 Cov.: 0 AF XY: 0.101 AC XY: 444 AN XY: 4412

African (AFR) AF: 0.00 AC: 0 AN: 4

American (AMR) AF: 0.00 AC: 0 AN: 4

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.0987 AC: 880 AN: 8920

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0143 AC: 1 AN: 70

Other (OTH) AF: 0.0370 AC: 2 AN: 54

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0635 AC: 9550 AN: 150454 Hom.: 390 Cov.: 31 AF XY: 0.0649 AC XY: 4758 AN XY: 73348

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0200 AC: 826 AN: 41260

American (AMR) AF: 0.0507 AC: 768 AN: 15152

Ashkenazi Jewish (ASJ) AF: 0.0950 AC: 327 AN: 3442

East Asian (EAS) AF: 0.0118 AC: 61 AN: 5162

South Asian (SAS) AF: 0.0933 AC: 439 AN: 4706

European-Finnish (FIN) AF: 0.136 AC: 1357 AN: 9974

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0820 AC: 5531 AN: 67472

Other (OTH) AF: 0.0570 AC: 119 AN: 2086

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.72

Splicing

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

Other links and lift over

dbSNP: rs8190866; hg19: chr8-18081202;