rs17443013

Variant names:

• chr4-41133527-T-C
• rs17443013
• NM_004307.2:c.-261+9460A>G

Variant summary

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

The NM_004307.2(APBB2):​c.-261+9460A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.446 in 151,970 control chromosomes in the GnomAD database, including 15,806 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 0.45 (15806 hom., cov: 32)
• Consequence: APBB2 NM_004307.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.90

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.636 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APBB2	NM_004307.2	c.-261+9460A>G		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+9460A>G		intron_variant	Intron 2 of 17	1	NM_004307.2	ENSP00000427211.1

Frequencies

GnomAD3 genomes AF: 0.446 AC: 67793 AN: 151852 Hom.: 15796 Cov.: 32

Gnomad AFR AF: 0.320

Gnomad AMI AF: 0.491

Gnomad AMR AF: 0.579

Gnomad ASJ AF: 0.447

Gnomad EAS AF: 0.655

Gnomad SAS AF: 0.555

Gnomad FIN AF: 0.503

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.466

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

GnomAD4 genome AF: 0.446 AC: 67827 AN: 151970 Hom.: 15806 Cov.: 32 AF XY: 0.455 AC XY: 33793 AN XY: 74256

Gnomad4 AFR AF: 0.320

Gnomad4 AMR AF: 0.580

Gnomad4 ASJ AF: 0.447

Gnomad4 EAS AF: 0.654

Gnomad4 SAS AF: 0.554

Gnomad4 FIN AF: 0.503

Gnomad4 NFE AF: 0.459

Gnomad4 OTH AF: 0.470

Alfa AF: 0.441 Hom.: 1947

Bravo AF: 0.446

Asia WGS AF: 0.574 AC: 1995 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.10
DANN	Benign	0.57

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: rs17443013; hg19: chr4-41135544;