chr4-41054699-A-G

Variant names:

• chr4-41054699-A-G
• rs114070671
• NM_004307.2:c.-51+10877T>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.-51+10877T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.021 in 152,272 control chromosomes in the GnomAD database, including 105 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 0.021 (105 hom., cov: 32)
• Consequence: APBB2 NM_004307.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0810
• Publications: 4 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0705 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APBB2	NM_004307.2	c.-51+10877T>C		intron_variant	Intron 4 of 17	ENST00000508593.6	NP_004298.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APBB2	ENST00000508593.6	c.-51+10877T>C		intron_variant	Intron 4 of 17	1	NM_004307.2	ENSP00000427211.1

Frequencies

GnomAD3 genomes AF: 0.0210 AC: 3188 AN: 152154 Hom.: 105 Cov.: 32

Gnomad AFR AF: 0.0728

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00733

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000382

Gnomad OTH AF: 0.0139

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

GnomAD4 genome AF: 0.0210 AC: 3191 AN: 152272 Hom.: 105 Cov.: 32 AF XY: 0.0203 AC XY: 1511 AN XY: 74446

African (AFR) AF: 0.0727 AC: 3020 AN: 41544

American (AMR) AF: 0.00732 AC: 112 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4818

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10614

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000382 AC: 26 AN: 68026

Other (OTH) AF: 0.0138 AC: 29 AN: 2106

Alfa AF: 0.0148 Hom.: 9

Bravo AF: 0.0234

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
DANN	Benign	0.49
PhyloP100		0.081
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: rs114070671; hg19: chr4-41056716;