rs16852584

chr4-40885974-A-C

Variant summary

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

The NM_004307.2(APBB2):c.1529+4390T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0688 in 152,098 control chromosomes in the GnomAD database, including 429 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 0.069 (429 hom., cov: 32)
• Consequence: APBB2 NM_004307.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.21

Genes affected

APBB2 (HGNC:582): (amyloid beta precursor protein binding family B member 2) The protein encoded by this gene interacts with the cytoplasmic domains of amyloid beta (A4) precursor protein and amyloid beta (A4) precursor-like protein 2. This protein contains two phosphotyrosine binding (PTB) domains, which are thought to function in signal transduction. Polymorphisms in this gene have been associated with Alzheimer's disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APBB2	NM_004307.2	c.1529+4390T>G		intron_variant		ENST00000508593.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APBB2	ENST00000508593.6	c.1529+4390T>G		intron_variant		1	NM_004307.2	P4

Frequencies

GnomAD3 genomes AF: 0.0689 AC: 10468 AN: 151980 Hom.: 430 Cov.: 32

Gnomad AFR AF: 0.0770

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0719

Gnomad ASJ AF: 0.129

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.0290

Gnomad FIN AF: 0.0962

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0557

Gnomad OTH AF: 0.0847

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

GnomAD4 genome AF: 0.0688 AC: 10462 AN: 152098 Hom.: 429 Cov.: 32 AF XY: 0.0698 AC XY: 5187 AN XY: 74350

Gnomad4 AFR AF: 0.0769

Gnomad4 AMR AF: 0.0718

Gnomad4 ASJ AF: 0.129

Gnomad4 EAS AF: 0.111

Gnomad4 SAS AF: 0.0292

Gnomad4 FIN AF: 0.0962

Gnomad4 NFE AF: 0.0557

Gnomad4 OTH AF: 0.0838

Alfa AF: 0.0604 Hom.: 403

Bravo AF: 0.0709

Asia WGS AF: 0.0590 AC: 204 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	5.5
Dann	Benign	0.64

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: rs16852584; hg19: chr4-40887991;