rs3850751

Variant names:

• chr8-18211655-T-C
• rs3850751
• NM_000662.8:c.-86+1475T>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.-86+1475T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 151,952 control chromosomes in the GnomAD database, including 10,554 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 0.35 (10554 hom., cov: 32)
• Consequence: NAT1 NM_000662.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.796
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.447 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAT1	NM_000662.8	c.-86+1475T>C		intron_variant	Intron 1 of 2	ENST00000307719.9	NP_000653.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAT1	ENST00000307719.9	c.-86+1475T>C		intron_variant	Intron 1 of 2	1	NM_000662.8	ENSP00000307218.4

Frequencies

GnomAD3 genomes AF: 0.351 AC: 53330 AN: 151834 Hom.: 10553 Cov.: 32

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.333

Gnomad AMR AF: 0.340

Gnomad ASJ AF: 0.456

Gnomad EAS AF: 0.325

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.464

Gnomad MID AF: 0.379

Gnomad NFE AF: 0.451

Gnomad OTH AF: 0.369

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

GnomAD4 genome AF: 0.351 AC: 53333 AN: 151952 Hom.: 10554 Cov.: 32 AF XY: 0.348 AC XY: 25834 AN XY: 74278

African (AFR) AF: 0.164 AC: 6818 AN: 41478

American (AMR) AF: 0.340 AC: 5180 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.456 AC: 1580 AN: 3466

East Asian (EAS) AF: 0.325 AC: 1676 AN: 5154

South Asian (SAS) AF: 0.282 AC: 1356 AN: 4810

European-Finnish (FIN) AF: 0.464 AC: 4894 AN: 10540

Middle Eastern (MID) AF: 0.377 AC: 110 AN: 292

European-Non Finnish (NFE) AF: 0.451 AC: 30638 AN: 67934

Other (OTH) AF: 0.368 AC: 779 AN: 2114

Alfa AF: 0.378 Hom.: 1568

Bravo AF: 0.333

Asia WGS AF: 0.274 AC: 954 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.76
DANN	Benign	0.52
PhyloP100		-0.80
PromoterAI		0.016	Neutral
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: rs3850751; hg19: chr8-18069164;