rs2585590

Positions:

• chr4-41142574-G-A
• chr4-41142574-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.-261+413C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.56 in 152,002 control chromosomes in the GnomAD database, including 24,224 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 0.56 (24224 hom., cov: 32)
• Consequence: APBB2 NM_004307.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.261

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.747 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APBB2	NM_004307.2	c.-261+413C>T		intron_variant		ENST00000508593.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APBB2	ENST00000508593.6	c.-261+413C>T		intron_variant		1	NM_004307.2	P4

Frequencies

GnomAD3 genomes AF: 0.560 AC: 85108 AN: 151884 Hom.: 24186 Cov.: 32

Gnomad AFR AF: 0.544

Gnomad AMI AF: 0.541

Gnomad AMR AF: 0.637

Gnomad ASJ AF: 0.557

Gnomad EAS AF: 0.767

Gnomad SAS AF: 0.709

Gnomad FIN AF: 0.556

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.527

Gnomad OTH AF: 0.569

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

GnomAD4 genome AF: 0.560 AC: 85197 AN: 152002 Hom.: 24224 Cov.: 32 AF XY: 0.571 AC XY: 42407 AN XY: 74282

Gnomad4 AFR AF: 0.545

Gnomad4 AMR AF: 0.638

Gnomad4 ASJ AF: 0.557

Gnomad4 EAS AF: 0.767

Gnomad4 SAS AF: 0.709

Gnomad4 FIN AF: 0.556

Gnomad4 NFE AF: 0.527

Gnomad4 OTH AF: 0.574

Alfa AF: 0.547 Hom.: 31240

Bravo AF: 0.565

Asia WGS AF: 0.732 AC: 2543 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.3
DANN	Benign	0.63

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: rs2585590; hg19: chr4-41144591;