chr4-41022934-T-C

Variant names:

• chr4-41022934-T-C
• rs951149
• NM_004307.2:c.20-8536A>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.20-8536A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.622 in 151,950 control chromosomes in the GnomAD database, including 29,713 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 0.62 (29713 hom., cov: 31)
• Consequence: APBB2 NM_004307.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.286
• 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 (EAS) allele frequency at 95% confidence interval = 0.695 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APBB2	NM_004307.2	MANE Select	c.20-8536A>G		intron	N/A	NP_004298.1	Q92870-4
	APBB2	NM_001166050.2		c.20-8536A>G		intron	N/A	NP_001159522.1	Q92870-1
	APBB2	NM_001330656.2		c.20-8536A>G		intron	N/A	NP_001317585.1	G5E9Y1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APBB2	ENST00000508593.6	TSL:1 MANE Select	c.20-8536A>G		intron	N/A	ENSP00000427211.1	Q92870-4
	APBB2	ENST00000513140.5	TSL:1	c.20-8536A>G		intron	N/A	ENSP00000426018.1	Q92870-2
	APBB2	ENST00000894650.1		c.20-8536A>G		intron	N/A	ENSP00000564709.1

Frequencies

GnomAD3 genomes AF: 0.622 AC: 94473 AN: 151832 Hom.: 29682 Cov.: 31

Gnomad AFR AF: 0.693

Gnomad AMI AF: 0.576

Gnomad AMR AF: 0.546

Gnomad ASJ AF: 0.571

Gnomad EAS AF: 0.715

Gnomad SAS AF: 0.535

Gnomad FIN AF: 0.661

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.594

Gnomad OTH AF: 0.596

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

GnomAD4 genome AF: 0.622 AC: 94556 AN: 151950 Hom.: 29713 Cov.: 31 AF XY: 0.623 AC XY: 46261 AN XY: 74276

African (AFR) AF: 0.693 AC: 28715 AN: 41432

American (AMR) AF: 0.546 AC: 8337 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.571 AC: 1982 AN: 3470

East Asian (EAS) AF: 0.715 AC: 3695 AN: 5170

South Asian (SAS) AF: 0.535 AC: 2574 AN: 4812

European-Finnish (FIN) AF: 0.661 AC: 6973 AN: 10552

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.594 AC: 40369 AN: 67932

Other (OTH) AF: 0.591 AC: 1249 AN: 2112

Alfa AF: 0.606 Hom.: 9776

Bravo AF: 0.614

Asia WGS AF: 0.620 AC: 2158 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.87
DANN	Benign	0.46
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: rs951149; hg19: chr4-41024951;