rs463164

Variant names:

• chr21-26206549-A-G
• rs463164
• ENST00000608591.5:n.183-8196A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

Genes affected

APP-DT (HGNC:55075): (APP divergent transcript)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000608591.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APP-DT	NR_186395.1		n.187-8196A>G		intron	N/A
	APP-DT	NR_186396.1		n.252-8196A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APP-DT	ENST00000608591.5	TSL:4	n.183-8196A>G		intron	N/A
	APP-DT	ENST00000609365.2	TSL:4	n.238-8196A>G		intron	N/A
	APP-DT	ENST00000717653.1		n.311-8196A>G		intron	N/A

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

African (AFR) AF: 0.130 AC: 5402 AN: 41512

American (AMR) AF: 0.203 AC: 3093 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 530 AN: 3470

East Asian (EAS) AF: 0.121 AC: 626 AN: 5162

South Asian (SAS) AF: 0.176 AC: 848 AN: 4818

European-Finnish (FIN) AF: 0.235 AC: 2484 AN: 10566

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.157 AC: 10641 AN: 67974

Other (OTH) AF: 0.151 AC: 318 AN: 2102

Alfa AF: 0.160 Hom.: 3307

Bravo AF: 0.156

Asia WGS AF: 0.130 AC: 457 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.8
DANN	Benign	0.87
PhyloP100		-0.51

Splicing

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

Other links and lift over

dbSNP: rs463164; hg19: chr21-27578868;