rs7823976

Positions:

• chr8-18194036-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001291962.2(NAT1):​c.-192-15745A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.425 in 152,040 control chromosomes in the GnomAD database, including 13,938 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 0.43 (13938 hom., cov: 31)
• Consequence: NAT1 NM_001291962.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.751

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.469 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NAT1	NM_001160179.3	c.-260-15745A>G		intron_variant
NAT1	NM_001291962.2	c.-192-15745A>G		intron_variant
NAT1	XM_047422397.1	c.-815-15745A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAT1	ENST00000517441.5	n.93-15745A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.425 AC: 64596 AN: 151922 Hom.: 13922 Cov.: 31

Gnomad AFR AF: 0.364

Gnomad AMI AF: 0.395

Gnomad AMR AF: 0.437

Gnomad ASJ AF: 0.407

Gnomad EAS AF: 0.416

Gnomad SAS AF: 0.278

Gnomad FIN AF: 0.410

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.474

Gnomad OTH AF: 0.443

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

GnomAD4 genome AF: 0.425 AC: 64628 AN: 152040 Hom.: 13938 Cov.: 31 AF XY: 0.418 AC XY: 31071 AN XY: 74308

Gnomad4 AFR AF: 0.364

Gnomad4 AMR AF: 0.437

Gnomad4 ASJ AF: 0.407

Gnomad4 EAS AF: 0.416

Gnomad4 SAS AF: 0.279

Gnomad4 FIN AF: 0.410

Gnomad4 NFE AF: 0.474

Gnomad4 OTH AF: 0.441

Alfa AF: 0.462 Hom.: 24330

Bravo AF: 0.426

Asia WGS AF: 0.335 AC: 1163 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.0
DANN	Benign	0.79

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7823976; hg19: chr8-18051545;