rs7003890

Variant names:

• chr8-18219801-T-C
• rs7003890
• NM_000662.8:c.-7+312T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 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=-0.85).
• 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 rank	MANE	Protein	UniProt
NAT1	NM_000662.8	c.-7+312T>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.-7+312T>C		intron_variant	Intron 2 of 2	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

African (AFR) AF: 0.368 AC: 15243 AN: 41474

American (AMR) AF: 0.485 AC: 7407 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.573 AC: 1988 AN: 3470

East Asian (EAS) AF: 0.443 AC: 2281 AN: 5148

South Asian (SAS) AF: 0.531 AC: 2561 AN: 4820

European-Finnish (FIN) AF: 0.499 AC: 5271 AN: 10554

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.544 AC: 36946 AN: 67958

Other (OTH) AF: 0.482 AC: 1020 AN: 2114

Alfa AF: 0.527 Hom.: 35963

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
PhyloP100		0.33
Mutation Taster		=100/0	polymorphism (auto)

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: rs7003890; hg19: chr8-18077310;