rs2830102

chr21-26162709-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.57+7855G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 149,814 control chromosomes in the GnomAD database, including 11,762 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 0.38 (11762 hom., cov: 25)
• Consequence: APP NM_000484.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.571 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APP	NM_000484.4	c.57+7855G>A		intron_variant		ENST00000346798.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APP	ENST00000346798.8	c.57+7855G>A		intron_variant		1	NM_000484.4
	ENST00000455275.1	n.177+4442C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.376 AC: 56347 AN: 149694 Hom.: 11753 Cov.: 25

Gnomad AFR AF: 0.578

Gnomad AMI AF: 0.371

Gnomad AMR AF: 0.335

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.253

Gnomad MID AF: 0.331

Gnomad NFE AF: 0.312

Gnomad OTH AF: 0.364

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

GnomAD4 genome AF: 0.376 AC: 56398 AN: 149814 Hom.: 11762 Cov.: 25 AF XY: 0.370 AC XY: 27021 AN XY: 73010

Gnomad4 AFR AF: 0.578

Gnomad4 AMR AF: 0.335

Gnomad4 ASJ AF: 0.267

Gnomad4 EAS AF: 0.209

Gnomad4 SAS AF: 0.239

Gnomad4 FIN AF: 0.253

Gnomad4 NFE AF: 0.312

Gnomad4 OTH AF: 0.361

Alfa AF: 0.352 Hom.: 1258

Bravo AF: 0.393

Asia WGS AF: 0.255 AC: 885 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.43
Dann	Benign	0.28

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: rs2830102; hg19: chr21-27535027;