rs2829984

Positions:

• chr21-25931939-C-T

Variant summary

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

The NM_000484.4(APP):​c.1688-19977G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 151,950 control chromosomes in the GnomAD database, including 7,680 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 0.24 (7680 hom., cov: 32)
• Consequence: APP NM_000484.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0900

Genes affected

APP (HGNC:620): (amyloid beta precursor protein) This gene encodes a cell surface receptor and transmembrane precursor protein that is cleaved by secretases to form a number of peptides. Some of these peptides are secreted and can bind to the acetyltransferase complex APBB1/TIP60 to promote transcriptional activation, while others form the protein basis of the amyloid plaques found in the brains of patients with Alzheimer disease. In addition, two of the peptides are antimicrobial peptides, having been shown to have bacteriocidal and antifungal activities. Mutations in this gene have been implicated in autosomal dominant Alzheimer disease and cerebroarterial amyloidosis (cerebral amyloid angiopathy). Multiple transcript variants encoding several different isoforms have been found for this gene. [provided by RefSeq, Aug 2014]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.558 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APP	NM_000484.4	c.1688-19977G>A		intron_variant		ENST00000346798.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APP	ENST00000346798.8	c.1688-19977G>A		intron_variant		1	NM_000484.4

Frequencies

GnomAD3 genomes AF: 0.244 AC: 37024 AN: 151832 Hom.: 7662 Cov.: 32

Gnomad AFR AF: 0.564

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.221

Gnomad ASJ AF: 0.0669

Gnomad EAS AF: 0.124

Gnomad SAS AF: 0.175

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.202

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

GnomAD4 genome AF: 0.244 AC: 37087 AN: 151950 Hom.: 7680 Cov.: 32 AF XY: 0.243 AC XY: 18015 AN XY: 74248

Gnomad4 AFR AF: 0.564

Gnomad4 AMR AF: 0.220

Gnomad4 ASJ AF: 0.0669

Gnomad4 EAS AF: 0.124

Gnomad4 SAS AF: 0.175

Gnomad4 FIN AF: 0.101

Gnomad4 NFE AF: 0.104

Gnomad4 OTH AF: 0.201

Alfa AF: 0.133 Hom.: 2919

Bravo AF: 0.265

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.4
DANN	Benign	0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs2829984; hg19: chr21-27304252;