rs7003890

Positions:

• chr8-18219801-T-C

Variant summary

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

The NM_000662.8(NAT1):​c.-7+312T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.482 in 152,008 control chromosomes in the GnomAD database, including 18,109 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 0.48 (18109 hom., cov: 32)
• Consequence: NAT1 NM_000662.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.326

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]

NAT1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.539 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NAT1	NM_000662.8	c.-7+312T>C		intron_variant		ENST00000307719.9	NP_000653.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NAT1	ENST00000307719.9	c.-7+312T>C		intron_variant		1	NM_000662.8	ENSP00000307218.4

Frequencies

GnomAD3 genomes AF: 0.482 AC: 73157 AN: 151888 Hom.: 18095 Cov.: 32

Gnomad AFR AF: 0.367

Gnomad AMI AF: 0.382

Gnomad AMR AF: 0.485

Gnomad ASJ AF: 0.573

Gnomad EAS AF: 0.443

Gnomad SAS AF: 0.530

Gnomad FIN AF: 0.499

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.544

Gnomad OTH AF: 0.487

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

GnomAD4 genome AF: 0.482 AC: 73216 AN: 152008 Hom.: 18109 Cov.: 32 AF XY: 0.480 AC XY: 35637 AN XY: 74286

Gnomad4 AFR AF: 0.368

Gnomad4 AMR AF: 0.485

Gnomad4 ASJ AF: 0.573

Gnomad4 EAS AF: 0.443

Gnomad4 SAS AF: 0.531

Gnomad4 FIN AF: 0.499

Gnomad4 NFE AF: 0.544

Gnomad4 OTH AF: 0.482

Alfa AF: 0.531 Hom.: 28820

Bravo AF: 0.473

Asia WGS AF: 0.469 AC: 1632 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	11
DANN	Benign	0.62

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

Publications

LitVar

Other links and lift over

dbSNP: rs7003890; hg19: chr8-18077310;