rs3850751

Positions:

• chr8-18211655-T-C

Variant summary

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

The ENST00000307719.9(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 ENST00000307719.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.796

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=-0.89).
• 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/exons	MANE	Protein	UniProt
NAT1	NM_000662.8	c.-86+1475T>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.-86+1475T>C		intron_variant		1	NM_000662.8	ENSP00000307218	P1

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

Gnomad4 AFR AF: 0.164

Gnomad4 AMR AF: 0.340

Gnomad4 ASJ AF: 0.456

Gnomad4 EAS AF: 0.325

Gnomad4 SAS AF: 0.282

Gnomad4 FIN AF: 0.464

Gnomad4 NFE AF: 0.451

Gnomad4 OTH AF: 0.368

Alfa AF: 0.387 Hom.: 1557

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

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: rs3850751; hg19: chr8-18069164;