rs4466078

Variant names:

• chr4-40971510-T-A
• rs4466078
• NM_004307.2:c.836-26437A>T

Your query was ambiguous. Multiple possible variants found:

• chr4-40971510-T-A
• chr4-40971510-T-C
• chr4-40971510-T-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.836-26437A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.951 in 152,310 control chromosomes in the GnomAD database, including 69,080 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 0.95 (69080 hom., cov: 32)
• Consequence: APBB2 NM_004307.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.223
• Publications: 8 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.985 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.836-26437A>T		intron	N/A	NP_004298.1	Q92870-4
	APBB2	NM_001166050.2		c.836-26440A>T		intron	N/A	NP_001159522.1	Q92870-1
	APBB2	NM_001330656.2		c.836-26440A>T		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.836-26437A>T		intron	N/A	ENSP00000427211.1	Q92870-4
	APBB2	ENST00000513140.5	TSL:1	c.836-26440A>T		intron	N/A	ENSP00000426018.1	Q92870-2
	APBB2	ENST00000894650.1		c.836-26437A>T		intron	N/A	ENSP00000564709.1

Frequencies

GnomAD3 genomes AF: 0.951 AC: 144747 AN: 152192 Hom.: 69036 Cov.: 32

Gnomad AFR AF: 0.875

Gnomad AMI AF: 0.997

Gnomad AMR AF: 0.927

Gnomad ASJ AF: 0.995

Gnomad EAS AF: 0.958

Gnomad SAS AF: 0.963

Gnomad FIN AF: 0.995

Gnomad MID AF: 0.994

Gnomad NFE AF: 0.991

Gnomad OTH AF: 0.954

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

GnomAD4 genome AF: 0.951 AC: 144844 AN: 152310 Hom.: 69080 Cov.: 32 AF XY: 0.951 AC XY: 70867 AN XY: 74482

African (AFR) AF: 0.876 AC: 36370 AN: 41536

American (AMR) AF: 0.927 AC: 14189 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.995 AC: 3453 AN: 3472

East Asian (EAS) AF: 0.958 AC: 4962 AN: 5180

South Asian (SAS) AF: 0.964 AC: 4654 AN: 4830

European-Finnish (FIN) AF: 0.995 AC: 10566 AN: 10618

Middle Eastern (MID) AF: 0.993 AC: 292 AN: 294

European-Non Finnish (NFE) AF: 0.991 AC: 67438 AN: 68046

Other (OTH) AF: 0.952 AC: 2011 AN: 2112

Alfa AF: 0.969 Hom.: 8343

Bravo AF: 0.942

Asia WGS AF: 0.914 AC: 3176 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	14
DANN	Benign	0.67
PhyloP100		0.22
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: rs4466078; hg19: chr4-40973527;