rs4646244

Positions:

• chr8-18390208-T-A

Variant summary

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

The XM_017012938.2(NAT2):​c.-7+3172T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 151,968 control chromosomes in the GnomAD database, including 5,744 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 0.27 (5744 hom., cov: 33)
• Consequence: NAT2 XM_017012938.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.221

Genes affected

NAT2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.333 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NAT2	XM_017012938.2	c.-7+3172T>A		intron_variant			XP_016868427.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.270 AC: 41020 AN: 151848 Hom.: 5744 Cov.: 33

Gnomad AFR AF: 0.256

Gnomad AMI AF: 0.496

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.315

Gnomad EAS AF: 0.264

Gnomad SAS AF: 0.349

Gnomad FIN AF: 0.237

Gnomad MID AF: 0.264

Gnomad NFE AF: 0.287

Gnomad OTH AF: 0.283

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

GnomAD4 genome AF: 0.270 AC: 41023 AN: 151968 Hom.: 5744 Cov.: 33 AF XY: 0.267 AC XY: 19801 AN XY: 74272

Gnomad4 AFR AF: 0.256

Gnomad4 AMR AF: 0.208

Gnomad4 ASJ AF: 0.315

Gnomad4 EAS AF: 0.265

Gnomad4 SAS AF: 0.346

Gnomad4 FIN AF: 0.237

Gnomad4 NFE AF: 0.287

Gnomad4 OTH AF: 0.281

Alfa AF: 0.275 Hom.: 743

Bravo AF: 0.262

Asia WGS AF: 0.308 AC: 1071 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.9
DANN	Benign	0.64

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4646244; hg19: chr8-18247718;