rs8190857

Variant names:

• chr8-18222012-A-C
• rs8190857
• NM_000662.8:c.-6-30A>C

Your query was ambiguous. Multiple possible variants found:

• chr8-18222012-A-C
• chr8-18222012-A-G
• chr8-18222012-A-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000662.8(NAT1):​c.-6-30A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000706 in 1,417,374 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. There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: NAT1 NM_000662.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.307
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 3 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAT1	NM_000662.8	c.-6-30A>C		intron_variant	Intron 2 of 2	ENST00000307719.9	NP_000653.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAT1	ENST00000307719.9	c.-6-30A>C		intron_variant	Intron 2 of 2	1	NM_000662.8	ENSP00000307218.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.06e-7 AC: 1 AN: 1417374 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 700712

African (AFR) AF: 0.00 AC: 0 AN: 31814

American (AMR) AF: 0.00 AC: 0 AN: 37828

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23290

East Asian (EAS) AF: 0.00 AC: 0 AN: 39292

South Asian (SAS) AF: 0.00 AC: 0 AN: 78202

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51902

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5478

European-Non Finnish (NFE) AF: 9.17e-7 AC: 1 AN: 1091084

Other (OTH) AF: 0.00 AC: 0 AN: 58484

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.4
DANN	Benign	0.76
PhyloP100		0.31
La Branchor		0.36
BranchPoint Hunter		3.0
PromoterAI		-0.0056	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: rs8190857; hg19: chr8-18079521;