rs3098914

Variant names:

• chr4-41074271-G-T
• rs3098914
• NM_004307.2:c.-148-8598C>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.-148-8598C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.303 in 151,930 control chromosomes in the GnomAD database, including 8,248 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 0.30 (8248 hom., cov: 33)
• Consequence: APBB2 NM_004307.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.61
• 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=-0.52).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.496 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004307.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APBB2	NM_004307.2	MANE Select	c.-148-8598C>A		intron	N/A	NP_004298.1
	APBB2	NM_001166050.2		c.-148-8598C>A		intron	N/A	NP_001159522.1
	APBB2	NM_001330656.2		c.-148-8598C>A		intron	N/A	NP_001317585.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APBB2	ENST00000508593.6	TSL:1 MANE Select	c.-148-8598C>A		intron	N/A	ENSP00000427211.1
	APBB2	ENST00000513140.5	TSL:1	c.-148-8598C>A		intron	N/A	ENSP00000426018.1
	APBB2	ENST00000295974.12	TSL:2	c.-148-8598C>A		intron	N/A	ENSP00000295974.8

Frequencies

GnomAD3 genomes AF: 0.303 AC: 45980 AN: 151814 Hom.: 8227 Cov.: 33

Gnomad AFR AF: 0.502

Gnomad AMI AF: 0.287

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.185

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.256

Gnomad FIN AF: 0.202

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.279

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

GnomAD4 genome AF: 0.303 AC: 46030 AN: 151930 Hom.: 8248 Cov.: 33 AF XY: 0.299 AC XY: 22220 AN XY: 74260

African (AFR) AF: 0.502 AC: 20784 AN: 41396

American (AMR) AF: 0.232 AC: 3545 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.185 AC: 640 AN: 3466

East Asian (EAS) AF: 0.125 AC: 648 AN: 5168

South Asian (SAS) AF: 0.255 AC: 1230 AN: 4820

European-Finnish (FIN) AF: 0.202 AC: 2127 AN: 10532

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.237 AC: 16133 AN: 67966

Other (OTH) AF: 0.277 AC: 585 AN: 2110

Alfa AF: 0.250 Hom.: 7715

Bravo AF: 0.311

Asia WGS AF: 0.189 AC: 655 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	13
DANN	Benign	0.68
PhyloP100		1.6
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: rs3098914; hg19: chr4-41076288;