8-18221342-A-T

Variant names:

• chr8-18221342-A-T
• rs8190851
• NM_000662.8:c.-6-700A>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_000662.8(NAT1):​c.-6-700A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.0000068 (0 hom., cov: 31)
  • Failed GnomAD Quality Control
• Consequence: NAT1 NM_000662.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.440
• Publications: 1 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.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000662.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAT1	NM_000662.8	MANE Select	c.-6-700A>T		intron	N/A	NP_000653.3
	NAT1	NM_001160175.4		c.181-700A>T		intron	N/A	NP_001153647.1
	NAT1	NM_001160176.4		c.181-700A>T		intron	N/A	NP_001153648.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAT1	ENST00000307719.9	TSL:1 MANE Select	c.-6-700A>T		intron	N/A	ENSP00000307218.4
	NAT1	ENST00000518029.5	TSL:1	c.-6-700A>T		intron	N/A	ENSP00000428270.1
	NAT1	ENST00000519006.5	TSL:1	n.522-700A>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00000676 AC: 1 AN: 148034 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000106

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000676 AC: 1 AN: 148034 Hom.: 0 Cov.: 31 AF XY: 0.0000139 AC XY: 1 AN XY: 71880

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

African (AFR) AF: 0.00 AC: 0 AN: 40218

American (AMR) AF: 0.00 AC: 0 AN: 14832

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3450

East Asian (EAS) AF: 0.00 AC: 0 AN: 5048

South Asian (SAS) AF: 0.00 AC: 0 AN: 4692

European-Finnish (FIN) AF: 0.000106 AC: 1 AN: 9452

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67078

Other (OTH) AF: 0.00 AC: 0 AN: 2042

⚠️ 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.

Alfa AF: 0.00 Hom.: 87

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.6
DANN	Benign	0.63
PhyloP100		-0.44
PromoterAI		0.011	Neutral

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: rs8190851; hg19: chr8-18078851;