11-6412919-C-G

Variant names:

• chr11-6412919-C-G
• rs4758416
• NM_001164.5:c.-14-1558G>C

Variant summary

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

The NM_001164.5(APBB1):​c.-14-1558G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.509 in 151,794 control chromosomes in the GnomAD database, including 21,846 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 0.51 (21846 hom., cov: 29)
• Consequence: APBB1 NM_001164.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0440
• Publications: 4 publications found

Genes affected

APBB1 (HGNC:581): (amyloid beta precursor protein binding family B member 1) The protein encoded by this gene is a member of the Fe65 protein family. It is an adaptor protein localized in the nucleus. It interacts with the Alzheimer's disease amyloid precursor protein (APP), transcription factor CP2/LSF/LBP1 and the low-density lipoprotein receptor-related protein. APP functions as a cytosolic anchoring site that can prevent the gene product's nuclear translocation. This encoded protein could play an important role in the pathogenesis of Alzheimer's disease. It is thought to regulate transcription. Also it is observed to block cell cycle progression by downregulating thymidylate synthase expression. Multiple alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Mar 2012]

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 (EAS) allele frequency at 95% confidence interval = 0.606 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APBB1	NM_001164.5	c.-14-1558G>C		intron_variant	Intron 1 of 14	ENST00000609360.6	NP_001155.1
APBB1	NM_145689.3	c.-14-1558G>C		intron_variant	Intron 1 of 13		NP_663722.1
APBB1	NR_047512.2	n.128-1558G>C		intron_variant	Intron 1 of 14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APBB1	ENST00000609360.6	c.-14-1558G>C		intron_variant	Intron 1 of 14	5	NM_001164.5	ENSP00000477213.1

Frequencies

GnomAD3 genomes AF: 0.509 AC: 77179 AN: 151676 Hom.: 21841 Cov.: 29

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.529

Gnomad AMR AF: 0.614

Gnomad ASJ AF: 0.689

Gnomad EAS AF: 0.621

Gnomad SAS AF: 0.599

Gnomad FIN AF: 0.558

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.611

Gnomad OTH AF: 0.577

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

GnomAD4 genome AF: 0.509 AC: 77208 AN: 151794 Hom.: 21846 Cov.: 29 AF XY: 0.511 AC XY: 37879 AN XY: 74176

African (AFR) AF: 0.244 AC: 10110 AN: 41370

American (AMR) AF: 0.614 AC: 9367 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.689 AC: 2386 AN: 3462

East Asian (EAS) AF: 0.620 AC: 3186 AN: 5136

South Asian (SAS) AF: 0.599 AC: 2874 AN: 4794

European-Finnish (FIN) AF: 0.558 AC: 5891 AN: 10548

Middle Eastern (MID) AF: 0.728 AC: 214 AN: 294

European-Non Finnish (NFE) AF: 0.611 AC: 41478 AN: 67914

Other (OTH) AF: 0.580 AC: 1222 AN: 2108

Alfa AF: 0.421 Hom.: 1291

Bravo AF: 0.502

Asia WGS AF: 0.606 AC: 2108 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.1
DANN	Benign	0.37
PhyloP100		0.044
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: rs4758416; hg19: chr11-6434149;