rs8078633

Variant names:

• chr17-60496504-C-G
• rs8078633
• NM_006380.5:c.228-1887G>C

Variant summary

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

The NM_006380.5(APPBP2):​c.228-1887G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 152,166 control chromosomes in the GnomAD database, including 10,325 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 0.20 (10325 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: APPBP2 NM_006380.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.451
• Publications: 4 publications found

Genes affected

APPBP2 (HGNC:622): (amyloid beta precursor protein binding protein 2) The protein encoded by this gene interacts with microtubules and is functionally associated with beta-amyloid precursor protein transport and/or processing. The beta-amyloid precursor protein is a cell surface protein with signal-transducing properties, and it is thought to play a role in the pathogenesis of Alzheimer's disease. The encoded protein may be involved in regulating cell death. This gene has been found to be highly expressed in breast cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.689 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APPBP2	NM_006380.5	c.228-1887G>C		intron_variant	Intron 2 of 12	ENST00000083182.8	NP_006371.2
APPBP2	NM_001282476.2	c.15-1887G>C		intron_variant	Intron 1 of 11		NP_001269405.1
APPBP2	XM_047435116.1	c.96-1887G>C		intron_variant	Intron 2 of 12		XP_047291072.1
APPBP2	XM_047435118.1	c.-123G>C		upstream_gene_variant			XP_047291074.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APPBP2	ENST00000083182.8	c.228-1887G>C		intron_variant	Intron 2 of 12	1	NM_006380.5	ENSP00000083182.3

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30607 AN: 152048 Hom.: 10282 Cov.: 32

Gnomad AFR AF: 0.695

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0817

Gnomad ASJ AF: 0.00374

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00331

Gnomad FIN AF: 0.000566

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.00343

Gnomad OTH AF: 0.145

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

GnomAD4 genome AF: 0.202 AC: 30702 AN: 152166 Hom.: 10325 Cov.: 32 AF XY: 0.194 AC XY: 14425 AN XY: 74424

African (AFR) AF: 0.696 AC: 28851 AN: 41458

American (AMR) AF: 0.0815 AC: 1246 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00374 AC: 13 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5186

South Asian (SAS) AF: 0.00269 AC: 13 AN: 4830

European-Finnish (FIN) AF: 0.000566 AC: 6 AN: 10606

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.00341 AC: 232 AN: 68006

Other (OTH) AF: 0.143 AC: 303 AN: 2114

Alfa AF: 0.157 Hom.: 757

Asia WGS AF: 0.0510 AC: 176 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.2
DANN	Benign	0.51
PhyloP100		-0.45
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8078633; hg19: chr17-58573865;