11-6395774-CTAG-C

Position:

• chr11-6395774-CTAG-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001164.5(APBB1):​c.1965+9_1965+11delCTA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 1,613,122 control chromosomes in the GnomAD database, including 19,806 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.16 (2133 hom., cov: 29)
  • Exomes 𝑓: 0.15 (17673 hom.)
• Consequence: APBB1 NM_001164.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.252

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.239 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APBB1	NM_001164.5	c.1965+9_1965+11delCTA		intron_variant		ENST00000609360.6	NP_001155.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APBB1	ENST00000609360.6	c.1965+9_1965+11delCTA		intron_variant		5	NM_001164.5	ENSP00000477213.1

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24403 AN: 151962 Hom.: 2124 Cov.: 29

Gnomad AFR AF: 0.221

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.00559

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.162

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.163

GnomAD3 exomes AF: 0.150 AC: 37393 AN: 249784 Hom.: 3325 AF XY: 0.154 AC XY: 20798 AN XY: 134990

Gnomad AFR exome AF: 0.225

Gnomad AMR exome AF: 0.145

Gnomad ASJ exome AF: 0.122

Gnomad EAS exome AF: 0.00691

Gnomad SAS exome AF: 0.263

Gnomad FIN exome AF: 0.107

Gnomad NFE exome AF: 0.143

Gnomad OTH exome AF: 0.158

GnomAD4 exome AF: 0.149 AC: 217161 AN: 1461042 Hom.: 17673 AF XY: 0.152 AC XY: 110429 AN XY: 726802

Gnomad4 AFR exome AF: 0.229

Gnomad4 AMR exome AF: 0.145

Gnomad4 ASJ exome AF: 0.123

Gnomad4 EAS exome AF: 0.00443

Gnomad4 SAS exome AF: 0.262

Gnomad4 FIN exome AF: 0.110

Gnomad4 NFE exome AF: 0.145

Gnomad4 OTH exome AF: 0.147

GnomAD4 genome AF: 0.161 AC: 24438 AN: 152080 Hom.: 2133 Cov.: 29 AF XY: 0.161 AC XY: 11963 AN XY: 74346

Gnomad4 AFR AF: 0.221

Gnomad4 AMR AF: 0.148

Gnomad4 ASJ AF: 0.110

Gnomad4 EAS AF: 0.00560

Gnomad4 SAS AF: 0.250

Gnomad4 FIN AF: 0.103

Gnomad4 NFE AF: 0.144

Gnomad4 OTH AF: 0.163

Alfa AF: 0.150 Hom.: 310

Bravo AF: 0.165

Asia WGS AF: 0.120 AC: 415 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1799755; hg19: chr11-6417004;