rs7665863

Variant names:

• chr4-41078877-A-G
• rs7665863
• NM_004307.2:c.-148-13204T>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.-148-13204T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 152,138 control chromosomes in the GnomAD database, including 1,963 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 0.15 (1963 hom., cov: 32)
• Consequence: APBB2 NM_004307.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.86
• Publications: 2 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APBB2	NM_004307.2	c.-148-13204T>C		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.-148-13204T>C		intron_variant	Intron 3 of 17	1	NM_004307.2	ENSP00000427211.1

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23184 AN: 152020 Hom.: 1961 Cov.: 32

Gnomad AFR AF: 0.0948

Gnomad AMI AF: 0.198

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.237

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.144

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

GnomAD4 genome AF: 0.152 AC: 23189 AN: 152138 Hom.: 1963 Cov.: 32 AF XY: 0.154 AC XY: 11426 AN XY: 74378

African (AFR) AF: 0.0947 AC: 3931 AN: 41522

American (AMR) AF: 0.135 AC: 2056 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 398 AN: 3472

East Asian (EAS) AF: 0.113 AC: 583 AN: 5176

South Asian (SAS) AF: 0.128 AC: 617 AN: 4822

European-Finnish (FIN) AF: 0.237 AC: 2508 AN: 10570

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.185 AC: 12583 AN: 67972

Other (OTH) AF: 0.143 AC: 301 AN: 2112

Alfa AF: 0.172 Hom.: 3709

Bravo AF: 0.143

Asia WGS AF: 0.127 AC: 441 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	12
DANN	Benign	0.40
PhyloP100		1.9
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: rs7665863; hg19: chr4-41080894;