rs7823976

Variant names:

• chr8-18194036-A-G
• rs7823976
• NM_001291962.2:c.-192-15745A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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 -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 rank	MANE	Protein	UniProt
NAT1	NM_001291962.2	c.-192-15745A>G		intron_variant	Intron 2 of 5		NP_001278891.1
NAT1	NM_001160179.3	c.-260-15745A>G		intron_variant	Intron 2 of 4		NP_001153651.1
NAT1	XM_047422397.1	c.-815-15745A>G		intron_variant	Intron 2 of 8		XP_047278353.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAT1	ENST00000517441.5	n.93-15745A>G		intron_variant	Intron 2 of 4	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

African (AFR) AF: 0.364 AC: 15076 AN: 41470

American (AMR) AF: 0.437 AC: 6668 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.407 AC: 1411 AN: 3464

East Asian (EAS) AF: 0.416 AC: 2148 AN: 5158

South Asian (SAS) AF: 0.279 AC: 1342 AN: 4812

European-Finnish (FIN) AF: 0.410 AC: 4342 AN: 10578

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.474 AC: 32204 AN: 67968

Other (OTH) AF: 0.441 AC: 930 AN: 2110

Alfa AF: 0.459 Hom.: 35760

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
PhyloP100		-0.75
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs7823976; hg19: chr8-18051545;