11-6395729-C-T

Variant names:

• chr11-6395729-C-T
• rs1800606
• NM_001164.5:c.1966-28G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 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=-0.94).
• 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 rank	MANE	Protein	UniProt
APBB1	NM_001164.5	c.1966-28G>A		intron_variant	Intron 14 of 14	ENST00000609360.6	NP_001155.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APBB1	ENST00000609360.6	c.1966-28G>A		intron_variant	Intron 14 of 14	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

GnomAD2 exomes AF: 0.862 AC: 207150 AN: 240364 AF XY: 0.855

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 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

African (AFR) AF: 0.919 AC: 30500 AN: 33174

American (AMR) AF: 0.863 AC: 37612 AN: 43600

Ashkenazi Jewish (ASJ) AF: 0.878 AC: 21819 AN: 24850

East Asian (EAS) AF: 0.996 AC: 39307 AN: 39478

South Asian (SAS) AF: 0.738 AC: 62120 AN: 84188

European-Finnish (FIN) AF: 0.890 AC: 47014 AN: 52808

Middle Eastern (MID) AF: 0.841 AC: 4778 AN: 5682

European-Non Finnish (NFE) AF: 0.855 AC: 942607 AN: 1102008

Other (OTH) AF: 0.864 AC: 51472 AN: 59608

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

African (AFR) AF: 0.919 AC: 38102 AN: 41446

American (AMR) AF: 0.868 AC: 13266 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.891 AC: 3092 AN: 3472

East Asian (EAS) AF: 0.995 AC: 5135 AN: 5162

South Asian (SAS) AF: 0.752 AC: 3623 AN: 4816

European-Finnish (FIN) AF: 0.897 AC: 9523 AN: 10620

Middle Eastern (MID) AF: 0.840 AC: 247 AN: 294

European-Non Finnish (NFE) AF: 0.856 AC: 58180 AN: 67944

Other (OTH) AF: 0.872 AC: 1836 AN: 2106

Alfa AF: 0.864 Hom.: 76388

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
PhyloP100		-1.3
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: rs1800606; hg19: chr11-6416959;