rs17680945

chr15-28947614-G-A

Variant summary

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

The NM_001353788.2(APBA2):c.-95+25865G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0508 in 152,182 control chromosomes in the GnomAD database, including 509 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 0.051 (509 hom., cov: 32)
• Consequence: APBA2 NM_001353788.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.211

Genes affected

APBA2 (HGNC:579): (amyloid beta precursor protein binding family A member 2) The protein encoded by this gene is a member of the X11 protein family. It is a neuronal adapter protein that interacts with the Alzheimer's disease amyloid precursor protein (APP). It stabilizes APP and inhibits production of proteolytic APP fragments including the A beta peptide that is deposited in the brains of Alzheimer's disease patients. This gene product is believed to be involved in signal transduction processes. It is also regarded as a putative vesicular trafficking protein in the brain that can form a complex with the potential to couple synaptic vesicle exocytosis to neuronal cell adhesion. [provided by RefSeq, Jul 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APBA2	NM_001353788.2	c.-95+25865G>A		intron_variant		ENST00000683413.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APBA2	ENST00000683413.1	c.-95+25865G>A		intron_variant			NM_001353788.2	P1

Frequencies

GnomAD3 genomes AF: 0.0507 AC: 7716 AN: 152064 Hom.: 508 Cov.: 32

Gnomad AFR AF: 0.0471

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.0903

Gnomad ASJ AF: 0.0193

Gnomad EAS AF: 0.328

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.0178

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0209

Gnomad OTH AF: 0.0482

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

GnomAD4 genome AF: 0.0508 AC: 7734 AN: 152182 Hom.: 509 Cov.: 32 AF XY: 0.0556 AC XY: 4137 AN XY: 74426

Gnomad4 AFR AF: 0.0471

Gnomad4 AMR AF: 0.0906

Gnomad4 ASJ AF: 0.0193

Gnomad4 EAS AF: 0.327

Gnomad4 SAS AF: 0.183

Gnomad4 FIN AF: 0.0178

Gnomad4 NFE AF: 0.0209

Gnomad4 OTH AF: 0.0529

Alfa AF: 0.0314 Hom.: 444

Bravo AF: 0.0539

Asia WGS AF: 0.281 AC: 976 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	4.3
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

Other links and lift over

dbSNP: rs17680945; hg19: chr15-29239817;