rs4466078

chr4-40971510-T-Achr4-40971510-T-Cchr4-40971510-T-G

Variant summary

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

The NM_004307.2(APBB2):c.836-26437A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.951 in 152,310 control chromosomes in the GnomAD database, including 69,080 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 0.95 (69080 hom., cov: 32)
• Consequence: APBB2 NM_004307.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.223

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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.985 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APBB2	NM_004307.2	c.836-26437A>T		intron_variant		ENST00000508593.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APBB2	ENST00000508593.6	c.836-26437A>T		intron_variant		1	NM_004307.2	P4

Frequencies

GnomAD3 genomes AF: 0.951 AC: 144747 AN: 152192 Hom.: 69036 Cov.: 32

Gnomad AFR AF: 0.875

Gnomad AMI AF: 0.997

Gnomad AMR AF: 0.927

Gnomad ASJ AF: 0.995

Gnomad EAS AF: 0.958

Gnomad SAS AF: 0.963

Gnomad FIN AF: 0.995

Gnomad MID AF: 0.994

Gnomad NFE AF: 0.991

Gnomad OTH AF: 0.954

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

GnomAD4 genome AF: 0.951 AC: 144844 AN: 152310 Hom.: 69080 Cov.: 32 AF XY: 0.951 AC XY: 70867 AN XY: 74482

Gnomad4 AFR AF: 0.876

Gnomad4 AMR AF: 0.927

Gnomad4 ASJ AF: 0.995

Gnomad4 EAS AF: 0.958

Gnomad4 SAS AF: 0.964

Gnomad4 FIN AF: 0.995

Gnomad4 NFE AF: 0.991

Gnomad4 OTH AF: 0.952

Alfa AF: 0.969 Hom.: 8343

Bravo AF: 0.942

Asia WGS AF: 0.914 AC: 3176 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	14
Dann	Benign	0.67

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: rs4466078; hg19: chr4-40973527;