4-41089818-T-C

Variant names:

• chr4-41089818-T-C
• rs9994615
• NM_004307.2:c.-149+10821A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004307.2(APBB2):​c.-149+10821A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 152,046 control chromosomes in the GnomAD database, including 8,894 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 0.34 (8894 hom., cov: 32)
• Consequence: APBB2 NM_004307.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.295
• 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APBB2	NM_004307.2	c.-149+10821A>G		intron_variant	Intron 3 of 17	ENST00000508593.6	NP_004298.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APBB2	ENST00000508593.6	c.-149+10821A>G		intron_variant	Intron 3 of 17	1	NM_004307.2	ENSP00000427211.1

Frequencies

GnomAD3 genomes AF: 0.338 AC: 51315 AN: 151928 Hom.: 8889 Cov.: 32

Gnomad AFR AF: 0.328

Gnomad AMI AF: 0.416

Gnomad AMR AF: 0.274

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.247

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.353

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.370

Gnomad OTH AF: 0.327

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

GnomAD4 genome AF: 0.338 AC: 51337 AN: 152046 Hom.: 8894 Cov.: 32 AF XY: 0.332 AC XY: 24646 AN XY: 74316

African (AFR) AF: 0.328 AC: 13590 AN: 41466

American (AMR) AF: 0.273 AC: 4173 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.322 AC: 1115 AN: 3466

East Asian (EAS) AF: 0.247 AC: 1281 AN: 5178

South Asian (SAS) AF: 0.248 AC: 1192 AN: 4812

European-Finnish (FIN) AF: 0.353 AC: 3731 AN: 10570

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.370 AC: 25127 AN: 67960

Other (OTH) AF: 0.323 AC: 681 AN: 2108

Alfa AF: 0.350 Hom.: 26485

Bravo AF: 0.331

Asia WGS AF: 0.246 AC: 855 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.1
DANN	Benign	0.74
PhyloP100		0.29
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: rs9994615; hg19: chr4-41091835;