rs8190865

chr8-18223689-A-Cchr8-18223689-A-Gchr8-18223689-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000662.8(NAT1):c.*769A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0123 in 129,410 control chromosomes in the GnomAD database, including 38 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 0.012 (38 hom., cov: 31)
  • Exomes 𝑓: 0.00066 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NAT1 NM_000662.8 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.406

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0123 (1586/129410) while in subpopulation AFR AF= 0.0396 (1508/38044). AF 95% confidence interval is 0.038. There are 38 homozygotes in gnomad4. There are 735 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd at 1590 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NAT1	NM_000662.8	c.*769A>C		3_prime_UTR_variant	3/3	ENST00000307719.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAT1	ENST00000307719.9	c.*769A>C		3_prime_UTR_variant	3/3	1	NM_000662.8	P1
NAT1	ENST00000518029.5	c.*769A>C		3_prime_UTR_variant	4/4	1		P1
NAT1	ENST00000517492.5	c.*769A>C		3_prime_UTR_variant	3/3	2		P1
NAT1	ENST00000545197.3			downstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.0123 AC: 1590 AN: 129282 Hom.: 38 Cov.: 31

Gnomad AFR AF: 0.0399

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00311

Gnomad ASJ AF: 0.000359

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000260

Gnomad FIN AF: 0.000139

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000356

Gnomad OTH AF: 0.00723

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000665 AC: 5 AN: 7520 Hom.: 0 Cov.: 0 AF XY: 0.000554 AC XY: 2 AN XY: 3612

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 FIN exome AF: 0.000676

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0123 AC: 1586 AN: 129410 Hom.: 38 Cov.: 31 AF XY: 0.0117 AC XY: 735 AN XY: 62906

Gnomad4 AFR AF: 0.0396

Gnomad4 AMR AF: 0.00311

Gnomad4 ASJ AF: 0.000359

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000261

Gnomad4 FIN AF: 0.000139

Gnomad4 NFE AF: 0.000356

Gnomad4 OTH AF: 0.00715

Alfa AF: 0.00278 Hom.: 3

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	1.8
Dann	Benign	0.42

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs8190865; hg19: chr8-18081198;