8-18223689-A-G

Variant names:

• chr8-18223689-A-G
• rs8190865
• NM_000662.8:c.*769A>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_000662.8(NAT1):​c.*769A>G variant causes a splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000077 in 129,826 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000077 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NAT1 NM_000662.8 splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.406
• 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BS2: High AC in GnomAd4 at 10 AD gene.

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.*769A>G		splice_region	Exon 3 of 3	NP_000653.3
	NAT1	NM_000662.8	MANE Select	c.*769A>G		3_prime_UTR	Exon 3 of 3	NP_000653.3
	NAT1	NM_001160175.4		c.*769A>G		splice_region	Exon 5 of 5	NP_001153647.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAT1	ENST00000307719.9	TSL:1 MANE Select	c.*769A>G		splice_region	Exon 3 of 3	ENSP00000307218.4
	NAT1	ENST00000518029.5	TSL:1	c.*769A>G		splice_region	Exon 4 of 4	ENSP00000428270.1
	NAT1	ENST00000307719.9	TSL:1 MANE Select	c.*769A>G		3_prime_UTR	Exon 3 of 3	ENSP00000307218.4

Frequencies

GnomAD3 genomes AF: 0.0000771 AC: 10 AN: 129698 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000522

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000370

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000533

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 7520 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 3612

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: 0.00 AC: 0 AN: 7400

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 62

Other (OTH) AF: 0.00 AC: 0 AN: 50

GnomAD4 genome AF: 0.0000770 AC: 10 AN: 129826 Hom.: 0 Cov.: 31 AF XY: 0.0000951 AC XY: 6 AN XY: 63080

African (AFR) AF: 0.0000521 AC: 2 AN: 38422

American (AMR) AF: 0.000369 AC: 5 AN: 13532

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2782

East Asian (EAS) AF: 0.00 AC: 0 AN: 5016

South Asian (SAS) AF: 0.00 AC: 0 AN: 3840

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7218

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 266

European-Non Finnish (NFE) AF: 0.0000533 AC: 3 AN: 56234

Other (OTH) AF: 0.00 AC: 0 AN: 1822

Alfa AF: 0.00 Hom.: 51

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.7
DANN	Benign	0.38
PhyloP100		-0.41

Splicing

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

Other links and lift over

dbSNP: rs8190865; hg19: chr8-18081198;