21-26171790-A-G

Variant names:

• chr21-26171790-A-G
• rs466448
• ENST00000455275.1:n.178-3820A>G

Variant summary

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

The ENST00000455275.1(ENSG00000224541):​n.178-3820A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.603 in 152,086 control chromosomes in the GnomAD database, including 29,725 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 0.60 (29725 hom., cov: 32)
• Consequence: ENSG00000224541 ENST00000455275.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.613
• Publications: 17 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.845 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APP-DT	NR_186395.1		n.186+738A>G		intron	N/A
	APP-DT	NR_186396.1		n.186+738A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000224541	ENST00000455275.1	TSL:2	n.178-3820A>G		intron	N/A
	APP-DT	ENST00000608591.5	TSL:4	n.182+738A>G		intron	N/A
	APP-DT	ENST00000609365.2	TSL:4	n.172+738A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.602 AC: 91536 AN: 151968 Hom.: 29668 Cov.: 32

Gnomad AFR AF: 0.852

Gnomad AMI AF: 0.579

Gnomad AMR AF: 0.646

Gnomad ASJ AF: 0.417

Gnomad EAS AF: 0.602

Gnomad SAS AF: 0.523

Gnomad FIN AF: 0.498

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.474

Gnomad OTH AF: 0.581

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

GnomAD4 genome AF: 0.603 AC: 91650 AN: 152086 Hom.: 29725 Cov.: 32 AF XY: 0.604 AC XY: 44899 AN XY: 74346

African (AFR) AF: 0.852 AC: 35365 AN: 41494

American (AMR) AF: 0.646 AC: 9879 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.417 AC: 1448 AN: 3470

East Asian (EAS) AF: 0.602 AC: 3104 AN: 5160

South Asian (SAS) AF: 0.521 AC: 2509 AN: 4816

European-Finnish (FIN) AF: 0.498 AC: 5266 AN: 10582

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.474 AC: 32189 AN: 67960

Other (OTH) AF: 0.577 AC: 1218 AN: 2110

Alfa AF: 0.518 Hom.: 72593

Bravo AF: 0.627

Asia WGS AF: 0.585 AC: 2036 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.97
DANN	Benign	0.59
PhyloP100		-0.61

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs466448;

hg19: chr21-27544108;