rs3098914

chr4-41074271-G-T

Variant summary

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

The NM_004307.2(APBB2):c.-148-8598C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.303 in 151,930 control chromosomes in the GnomAD database, including 8,248 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 0.30 (8248 hom., cov: 33)
• Consequence: APBB2 NM_004307.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.61

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=-0.52).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.496 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APBB2	NM_004307.2	c.-148-8598C>A		intron_variant		ENST00000508593.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APBB2	ENST00000508593.6	c.-148-8598C>A		intron_variant		1	NM_004307.2	P4

Frequencies

GnomAD3 genomes AF: 0.303 AC: 45980 AN: 151814 Hom.: 8227 Cov.: 33

Gnomad AFR AF: 0.502

Gnomad AMI AF: 0.287

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.185

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.256

Gnomad FIN AF: 0.202

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.279

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

GnomAD4 genome AF: 0.303 AC: 46030 AN: 151930 Hom.: 8248 Cov.: 33 AF XY: 0.299 AC XY: 22220 AN XY: 74260

Gnomad4 AFR AF: 0.502

Gnomad4 AMR AF: 0.232

Gnomad4 ASJ AF: 0.185

Gnomad4 EAS AF: 0.125

Gnomad4 SAS AF: 0.255

Gnomad4 FIN AF: 0.202

Gnomad4 NFE AF: 0.237

Gnomad4 OTH AF: 0.277

Alfa AF: 0.248 Hom.: 6374

Bravo AF: 0.311

Asia WGS AF: 0.189 AC: 655 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
Cadd	Benign	13
Dann	Benign	0.68

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: rs3098914; hg19: chr4-41076288;