rs10015784

chr4-41097204-G-Achr4-41097204-G-C

Variant summary

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

The NM_004307.2(APBB2):c.-149+3435C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.434 in 151,888 control chromosomes in the GnomAD database, including 14,679 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 0.43 (14679 hom., cov: 32)
• Consequence: APBB2 NM_004307.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.733

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.475 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APBB2	NM_004307.2	c.-149+3435C>T		intron_variant		ENST00000508593.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APBB2	ENST00000508593.6	c.-149+3435C>T		intron_variant		1	NM_004307.2	P4

Frequencies

GnomAD3 genomes AF: 0.434 AC: 65896 AN: 151770 Hom.: 14664 Cov.: 32

Gnomad AFR AF: 0.413

Gnomad AMI AF: 0.448

Gnomad AMR AF: 0.353

Gnomad ASJ AF: 0.450

Gnomad EAS AF: 0.279

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.481

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.479

Gnomad OTH AF: 0.425

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

GnomAD4 genome AF: 0.434 AC: 65947 AN: 151888 Hom.: 14679 Cov.: 32 AF XY: 0.426 AC XY: 31644 AN XY: 74214

Gnomad4 AFR AF: 0.413

Gnomad4 AMR AF: 0.352

Gnomad4 ASJ AF: 0.450

Gnomad4 EAS AF: 0.280

Gnomad4 SAS AF: 0.301

Gnomad4 FIN AF: 0.481

Gnomad4 NFE AF: 0.479

Gnomad4 OTH AF: 0.425

Alfa AF: 0.442 Hom.: 14630

Bravo AF: 0.424

Asia WGS AF: 0.330 AC: 1146 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	0.19
Dann	Benign	0.80

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: rs10015784; hg19: chr4-41099221;