rs463164

Positions:

• chr21-26206549-A-G

Variant summary

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

The ENST00000608591.5(APP-DT):​n.183-8196A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 152,064 control chromosomes in the GnomAD database, including 2,044 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 0.16 (2044 hom., cov: 32)
• Consequence: APP-DT ENST00000608591.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.507

Genes affected

APP-DT (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APP-DT	NR_186395.1	n.187-8196A>G		intron_variant
APP-DT	NR_186396.1	n.252-8196A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APP-DT	ENST00000608591.5	n.183-8196A>G		intron_variant		4
APP-DT	ENST00000609365.2	n.238-8196A>G		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24132 AN: 151946 Hom.: 2039 Cov.: 32

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.187

Gnomad AMR AF: 0.203

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.176

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.154

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

GnomAD4 genome AF: 0.159 AC: 24162 AN: 152064 Hom.: 2044 Cov.: 32 AF XY: 0.163 AC XY: 12144 AN XY: 74314

Gnomad4 AFR AF: 0.130

Gnomad4 AMR AF: 0.203

Gnomad4 ASJ AF: 0.153

Gnomad4 EAS AF: 0.121

Gnomad4 SAS AF: 0.176

Gnomad4 FIN AF: 0.235

Gnomad4 NFE AF: 0.157

Gnomad4 OTH AF: 0.151

Alfa AF: 0.161 Hom.: 2639

Bravo AF: 0.156

Asia WGS AF: 0.130 AC: 457 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.8
DANN	Benign	0.87

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs463164; hg19: chr21-27578868;