21-26171645-A-G

Variant names:

• chr21-26171645-A-G
• rs466433
• ENST00000455275.1:n.178-3965A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000455275.1(ENSG00000224541):​n.178-3965A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0832 in 152,170 control chromosomes in the GnomAD database, including 960 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 0.083 (960 hom., cov: 31)
• Consequence: ENSG00000224541 ENST00000455275.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.55
• Publications: 13 publications found

Genes affected

ENSG00000224541 (HGNC:):

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.193 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000455275.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APP-DT	NR_186395.1		n.186+593A>G		intron	N/A
	APP-DT	NR_186396.1		n.186+593A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000224541	ENST00000455275.1	TSL:2	n.178-3965A>G		intron	N/A
	APP-DT	ENST00000608591.5	TSL:4	n.182+593A>G		intron	N/A
	APP-DT	ENST00000609365.2	TSL:4	n.172+593A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0832 AC: 12644 AN: 152052 Hom.: 956 Cov.: 31

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0675

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.203

Gnomad SAS AF: 0.0773

Gnomad FIN AF: 0.0653

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0239

Gnomad OTH AF: 0.0742

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

GnomAD4 genome AF: 0.0832 AC: 12663 AN: 152170 Hom.: 960 Cov.: 31 AF XY: 0.0847 AC XY: 6301 AN XY: 74406

African (AFR) AF: 0.186 AC: 7711 AN: 41478

American (AMR) AF: 0.0682 AC: 1042 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00346 AC: 12 AN: 3470

East Asian (EAS) AF: 0.203 AC: 1049 AN: 5168

South Asian (SAS) AF: 0.0767 AC: 370 AN: 4822

European-Finnish (FIN) AF: 0.0653 AC: 693 AN: 10610

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0239 AC: 1626 AN: 68018

Other (OTH) AF: 0.0735 AC: 155 AN: 2110

Alfa AF: 0.0493 Hom.: 583

Bravo AF: 0.0893

Asia WGS AF: 0.142 AC: 493 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.28
DANN	Benign	0.65
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs466433; hg19: chr21-27543963;