21-26170924-AC-A

Position:

• chr21-26170924-AC-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001136131.3(APP):​c.-49+60delG variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 1.0 (76032 hom., cov: 0)
  • Exomes 𝑓: 1.0 (75839 hom.)
• Consequence: APP NM_001136131.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00

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]

APP-DT (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 21-26170924-AC-A is Benign according to our data. Variant chr21-26170924-AC-A is described in ClinVar as [Benign]. Clinvar id is 1241577.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.994 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APP	NM_001136131.3	c.-49+60delG		intron_variant			NP_001129603.1
APP-DT	NR_186395.1	n.59delC		non_coding_transcript_exon_variant	1/3
APP-DT	NR_186396.1	n.59delC		non_coding_transcript_exon_variant	1/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APP	ENST00000359726.7	c.-49+60delG		intron_variant		2		ENSP00000352760.4
APP-DT	ENST00000608591.5	n.55delC		non_coding_transcript_exon_variant	1/3	4
APP-DT	ENST00000609365.2	n.45delC		non_coding_transcript_exon_variant	1/4	4

Frequencies

GnomAD3 genomes AF: 1.00 AC: 151958 AN: 151962 Hom.: 75977 Cov.: 0

Gnomad AFR AF: 1.00

Gnomad AMI AF: 1.00

Gnomad AMR AF: 1.00

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 1.00

Gnomad NFE AF: 1.00

Gnomad OTH AF: 1.00

GnomAD4 exome AF: 1.00 AC: 151682 AN: 151686 Hom.: 75839 Cov.: 0 AF XY: 1.00 AC XY: 77449 AN XY: 77450

Gnomad4 AFR exome AF: 1.00

Gnomad4 AMR exome AF: 1.00

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 1.00 AC: 152068 AN: 152072 Hom.: 76032 Cov.: 0 AF XY: 1.00 AC XY: 74330 AN XY: 74334

Gnomad4 AFR AF: 1.00

Gnomad4 AMR AF: 1.00

Gnomad4 ASJ AF: 1.00

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 1.00

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 1.00

Gnomad4 OTH AF: 1.00

Alfa AF: 0.671 Hom.: 2235

Bravo AF: 1.00

Asia WGS AF: 1.00 AC: 3469 AN: 3470

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 14, 2019

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11299404; hg19: chr21-27543242;