rs1873283

Positions:

• chr15-29046299-C-T

Variant summary

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

The NM_001353788.2(APBA2):​c.-40-7546C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 152,124 control chromosomes in the GnomAD database, including 6,280 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 0.22 (6280 hom., cov: 32)
• Consequence: APBA2 NM_001353788.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.280

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]

APBA2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.498 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APBA2	NM_001353788.2	c.-40-7546C>T		intron_variant		ENST00000683413.1	NP_001340717.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APBA2	ENST00000683413.1	c.-40-7546C>T		intron_variant			NM_001353788.2	ENSP00000507394.1

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33857 AN: 152006 Hom.: 6258 Cov.: 32

Gnomad AFR AF: 0.504

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.277

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.0863

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0854

Gnomad OTH AF: 0.189

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

GnomAD4 genome AF: 0.223 AC: 33927 AN: 152124 Hom.: 6280 Cov.: 32 AF XY: 0.222 AC XY: 16487 AN XY: 74362

Gnomad4 AFR AF: 0.504

Gnomad4 AMR AF: 0.191

Gnomad4 ASJ AF: 0.101

Gnomad4 EAS AF: 0.277

Gnomad4 SAS AF: 0.226

Gnomad4 FIN AF: 0.0863

Gnomad4 NFE AF: 0.0854

Gnomad4 OTH AF: 0.193

Alfa AF: 0.116 Hom.: 2386

Bravo AF: 0.242

Asia WGS AF: 0.315 AC: 1094 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.8
DANN	Benign	0.79

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: rs1873283; hg19: chr15-29338502;