rs7697609

Variant names:

• chr4-40954557-C-T
• rs7697609
• NM_004307.2:c.836-9484G>A

Variant summary

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

The NM_004307.2(APBB2):​c.836-9484G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 152,132 control chromosomes in the GnomAD database, including 3,794 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 (3794 hom., cov: 32)
• Consequence: APBB2 NM_004307.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.67
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APBB2	NM_004307.2	c.836-9484G>A		intron_variant	Intron 6 of 17	ENST00000508593.6	NP_004298.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APBB2	ENST00000508593.6	c.836-9484G>A		intron_variant	Intron 6 of 17	1	NM_004307.2	ENSP00000427211.1

Frequencies

GnomAD3 genomes AF: 0.214 AC: 32510 AN: 152014 Hom.: 3786 Cov.: 32

Gnomad AFR AF: 0.279

Gnomad AMI AF: 0.276

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.0194

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.215

Gnomad OTH AF: 0.200

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

GnomAD4 genome AF: 0.214 AC: 32543 AN: 152132 Hom.: 3794 Cov.: 32 AF XY: 0.209 AC XY: 15565 AN XY: 74388

African (AFR) AF: 0.279 AC: 11570 AN: 41494

American (AMR) AF: 0.149 AC: 2271 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.192 AC: 668 AN: 3472

East Asian (EAS) AF: 0.0193 AC: 100 AN: 5184

South Asian (SAS) AF: 0.126 AC: 609 AN: 4824

European-Finnish (FIN) AF: 0.188 AC: 1991 AN: 10566

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.215 AC: 14607 AN: 67998

Other (OTH) AF: 0.197 AC: 416 AN: 2110

Alfa AF: 0.212 Hom.: 14935

Bravo AF: 0.213

Asia WGS AF: 0.0760 AC: 267 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.019
DANN	Benign	0.59
PhyloP100		-2.7
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: rs7697609; hg19: chr4-40956574;