chr11-6412919-C-G

Position:

• chr11-6412919-C-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
APBB1	NM_001164.5	c.-14-1558G>C		intron_variant		ENST00000609360.6	NP_001155.1
APBB1	NM_145689.3	c.-14-1558G>C		intron_variant			NP_663722.1
APBB1	NR_047512.2	n.128-1558G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APBB1	ENST00000609360.6	c.-14-1558G>C		intron_variant		5	NM_001164.5	ENSP00000477213	A1

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

Gnomad4 AFR AF: 0.244

Gnomad4 AMR AF: 0.614

Gnomad4 ASJ AF: 0.689

Gnomad4 EAS AF: 0.620

Gnomad4 SAS AF: 0.599

Gnomad4 FIN AF: 0.558

Gnomad4 NFE AF: 0.611

Gnomad4 OTH AF: 0.580

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

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: rs4758416; hg19: chr11-6434149;