rs4646267

Positions:

• chr8-18390403-A-G
• chr8-18390403-A-T

Variant summary

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

The XM_017012938.2(NAT2):​c.-7+3367A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 152,174 control chromosomes in the GnomAD database, including 2,691 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 0.17 (2691 hom., cov: 32)
• Consequence: NAT2 XM_017012938.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.499

Genes affected

NAT2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.469 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NAT2	XM_017012938.2	c.-7+3367A>G		intron_variant			XP_016868427.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25789 AN: 152058 Hom.: 2691 Cov.: 32

Gnomad AFR AF: 0.0969

Gnomad AMI AF: 0.161

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.0937

Gnomad EAS AF: 0.486

Gnomad SAS AF: 0.147

Gnomad FIN AF: 0.225

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.151

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

GnomAD4 genome AF: 0.170 AC: 25798 AN: 152174 Hom.: 2691 Cov.: 32 AF XY: 0.174 AC XY: 12936 AN XY: 74396

Gnomad4 AFR AF: 0.0968

Gnomad4 AMR AF: 0.231

Gnomad4 ASJ AF: 0.0937

Gnomad4 EAS AF: 0.485

Gnomad4 SAS AF: 0.147

Gnomad4 FIN AF: 0.225

Gnomad4 NFE AF: 0.174

Gnomad4 OTH AF: 0.156

Alfa AF: 0.168 Hom.: 2931

Bravo AF: 0.171

Asia WGS AF: 0.288 AC: 1005 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	7.7
DANN	Benign	0.95

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4646267; hg19: chr8-18247913;