rs2585590

Variant names:

• chr4-41142574-G-A
• rs2585590
• NM_004307.2:c.-261+413C>T

Your query was ambiguous. Multiple possible variants found:

• chr4-41142574-G-A
• chr4-41142574-G-C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
APBB2	NM_004307.2	c.-261+413C>T		intron_variant	Intron 2 of 17	ENST00000508593.6	NP_004298.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APBB2	ENST00000508593.6	c.-261+413C>T		intron_variant	Intron 2 of 17	1	NM_004307.2	ENSP00000427211.1

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

African (AFR) AF: 0.545 AC: 22591 AN: 41456

American (AMR) AF: 0.638 AC: 9744 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.557 AC: 1930 AN: 3468

East Asian (EAS) AF: 0.767 AC: 3957 AN: 5162

South Asian (SAS) AF: 0.709 AC: 3419 AN: 4824

European-Finnish (FIN) AF: 0.556 AC: 5863 AN: 10538

Middle Eastern (MID) AF: 0.619 AC: 182 AN: 294

European-Non Finnish (NFE) AF: 0.527 AC: 35810 AN: 67972

Other (OTH) AF: 0.574 AC: 1211 AN: 2110

Alfa AF: 0.546 Hom.: 36925

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
PhyloP100		0.26
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2585590; hg19: chr4-41144591;