chr4-41000929-G-C

Variant names:

• chr4-41000929-G-C
• rs13133980
• NM_004307.2:c.835+12654C>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004307.2(APBB2):​c.835+12654C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.482 in 152,000 control chromosomes in the GnomAD database, including 19,552 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 0.48 (19552 hom., cov: 31)
• Consequence: APBB2 NM_004307.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.60

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.694 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APBB2	NM_004307.2	c.835+12654C>G		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.835+12654C>G		intron_variant	Intron 6 of 17	1	NM_004307.2	ENSP00000427211.1

Frequencies

GnomAD3 genomes AF: 0.483 AC: 73334 AN: 151880 Hom.: 19560 Cov.: 31

Gnomad AFR AF: 0.241

Gnomad AMI AF: 0.571

Gnomad AMR AF: 0.488

Gnomad ASJ AF: 0.568

Gnomad EAS AF: 0.713

Gnomad SAS AF: 0.524

Gnomad FIN AF: 0.645

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.578

Gnomad OTH AF: 0.487

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

GnomAD4 genome AF: 0.482 AC: 73340 AN: 152000 Hom.: 19552 Cov.: 31 AF XY: 0.488 AC XY: 36243 AN XY: 74322

Gnomad4 AFR AF: 0.241

Gnomad4 AMR AF: 0.487

Gnomad4 ASJ AF: 0.568

Gnomad4 EAS AF: 0.713

Gnomad4 SAS AF: 0.524

Gnomad4 FIN AF: 0.645

Gnomad4 NFE AF: 0.578

Gnomad4 OTH AF: 0.483

Alfa AF: 0.386 Hom.: 1170

Bravo AF: 0.458

Asia WGS AF: 0.588 AC: 2045 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.4
DANN	Benign	0.46

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

Publications

LitVar

Other links and lift over

dbSNP: rs13133980; hg19: chr4-41002946;