4-41080466-G-C

Variant names:

• chr4-41080466-G-C
• rs10516997
• NM_004307.2:c.-148-14793C>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.-148-14793C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 152,150 control chromosomes in the GnomAD database, including 3,508 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 0.21 (3508 hom., cov: 32)
• Consequence: APBB2 NM_004307.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.778
• Publications: 3 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 (AMR) allele frequency at 95% confidence interval = 0.24 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APBB2	NM_004307.2	c.-148-14793C>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.-148-14793C>G		intron_variant	Intron 3 of 17	1	NM_004307.2	ENSP00000427211.1

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31554 AN: 152032 Hom.: 3506 Cov.: 32

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.321

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.0402

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.168

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.235

Gnomad OTH AF: 0.195

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

GnomAD4 genome AF: 0.207 AC: 31561 AN: 152150 Hom.: 3508 Cov.: 32 AF XY: 0.204 AC XY: 15146 AN XY: 74358

African (AFR) AF: 0.181 AC: 7502 AN: 41516

American (AMR) AF: 0.246 AC: 3765 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.183 AC: 636 AN: 3472

East Asian (EAS) AF: 0.0401 AC: 208 AN: 5182

South Asian (SAS) AF: 0.189 AC: 909 AN: 4810

European-Finnish (FIN) AF: 0.168 AC: 1775 AN: 10562

Middle Eastern (MID) AF: 0.248 AC: 72 AN: 290

European-Non Finnish (NFE) AF: 0.235 AC: 15989 AN: 68006

Other (OTH) AF: 0.196 AC: 413 AN: 2110

Alfa AF: 0.126 Hom.: 226

Bravo AF: 0.209

Asia WGS AF: 0.118 AC: 412 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	0.71
DANN	Benign	0.51
PhyloP100		-0.78
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: rs10516997; hg19: chr4-41082483;