rs9984764

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The ENST00000346798.8(APP):​c.58-13034C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0106 in 152,260 control chromosomes in the GnomAD database, including 19 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 0.011 ( 19 hom., cov: 32)

Consequence

APP
ENST00000346798.8 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.171
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0106 (1615/152260) while in subpopulation AFR AF= 0.0348 (1444/41522). AF 95% confidence interval is 0.0333. There are 19 homozygotes in gnomad4. There are 791 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 1615 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
APPNM_000484.4 linkuse as main transcriptc.58-13034C>T intron_variant ENST00000346798.8 NP_000475.1
LOC124900466XR_007067829.1 linkuse as main transcriptn.8004-2198C>T intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
APPENST00000346798.8 linkuse as main transcriptc.58-13034C>T intron_variant 1 NM_000484.4 ENSP00000284981 P05067-1

Frequencies

GnomAD3 genomes
AF:
0.0106
AC:
1608
AN:
152142
Hom.:
19
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0347
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00556
Gnomad ASJ
AF:
0.0107
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000353
Gnomad OTH
AF:
0.0110
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.0106
AC:
1615
AN:
152260
Hom.:
19
Cov.:
32
AF XY:
0.0106
AC XY:
791
AN XY:
74460
show subpopulations
Gnomad4 AFR
AF:
0.0348
Gnomad4 AMR
AF:
0.00555
Gnomad4 ASJ
AF:
0.0107
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000353
Gnomad4 OTH
AF:
0.0109
Alfa
AF:
0.00243
Hom.:
5
Bravo
AF:
0.0122
Asia WGS
AF:
0.00375
AC:
14
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.85
CADD
Benign
4.4
DANN
Benign
0.56

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs9984764; hg19: chr21-27497497; API