11-6395729-C-T

Position:

• chr11-6395729-C-T

Variant summary

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

The NM_001164.5(APBB1):​c.1966-28G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.858 in 1,597,460 control chromosomes in the GnomAD database, including 589,899 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 0.88 (58988 hom., cov: 31)
  • Exomes 𝑓: 0.86 (530911 hom.)
• Consequence: APBB1 NM_001164.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27

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]

APBB1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.972 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APBB1	NM_001164.5	c.1966-28G>A		intron_variant		ENST00000609360.6	NP_001155.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APBB1	ENST00000609360.6	c.1966-28G>A		intron_variant		5	NM_001164.5	ENSP00000477213.1

Frequencies

GnomAD3 genomes AF: 0.880 AC: 133713 AN: 151946 Hom.: 58945 Cov.: 31

Gnomad AFR AF: 0.919

Gnomad AMI AF: 0.884

Gnomad AMR AF: 0.868

Gnomad ASJ AF: 0.891

Gnomad EAS AF: 0.995

Gnomad SAS AF: 0.753

Gnomad FIN AF: 0.897

Gnomad MID AF: 0.826

Gnomad NFE AF: 0.856

Gnomad OTH AF: 0.873

GnomAD3 exomes AF: 0.862 AC: 207150 AN: 240364 Hom.: 89727 AF XY: 0.855 AC XY: 110732 AN XY: 129562

Gnomad AFR exome AF: 0.921

Gnomad AMR exome AF: 0.861

Gnomad ASJ exome AF: 0.878

Gnomad EAS exome AF: 0.993

Gnomad SAS exome AF: 0.737

Gnomad FIN exome AF: 0.892

Gnomad NFE exome AF: 0.858

Gnomad OTH exome AF: 0.848

GnomAD4 exome AF: 0.856 AC: 1237229 AN: 1445396 Hom.: 530911 Cov.: 64 AF XY: 0.852 AC XY: 610889 AN XY: 716928

Gnomad4 AFR exome AF: 0.919

Gnomad4 AMR exome AF: 0.863

Gnomad4 ASJ exome AF: 0.878

Gnomad4 EAS exome AF: 0.996

Gnomad4 SAS exome AF: 0.738

Gnomad4 FIN exome AF: 0.890

Gnomad4 NFE exome AF: 0.855

Gnomad4 OTH exome AF: 0.864

GnomAD4 genome AF: 0.880 AC: 133810 AN: 152064 Hom.: 58988 Cov.: 31 AF XY: 0.879 AC XY: 65318 AN XY: 74346

Gnomad4 AFR AF: 0.919

Gnomad4 AMR AF: 0.868

Gnomad4 ASJ AF: 0.891

Gnomad4 EAS AF: 0.995

Gnomad4 SAS AF: 0.752

Gnomad4 FIN AF: 0.897

Gnomad4 NFE AF: 0.856

Gnomad4 OTH AF: 0.872

Alfa AF: 0.861 Hom.: 58918

Bravo AF: 0.883

Asia WGS AF: 0.892 AC: 3104 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.89
DANN	Benign	0.72

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: rs1800606; hg19: chr11-6416959;