rs1079199

Positions:

• chr11-6406876-T-C

Variant summary

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

The NM_001164.5(APBB1):​c.722-3054A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 152,064 control chromosomes in the GnomAD database, including 9,667 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 0.34 (9667 hom., cov: 32)
• Consequence: APBB1 NM_001164.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0670

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.473 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APBB1	NM_001164.5	c.722-3054A>G		intron_variant		ENST00000609360.6
APBB1	NM_145689.3	c.722-3054A>G		intron_variant
APBB1	NR_047512.2	n.863-3054A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APBB1	ENST00000609360.6	c.722-3054A>G		intron_variant		5	NM_001164.5	A1

Frequencies

GnomAD3 genomes AF: 0.343 AC: 52079 AN: 151946 Hom.: 9654 Cov.: 32

Gnomad AFR AF: 0.479

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.128

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.343

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.335

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

GnomAD4 genome AF: 0.343 AC: 52123 AN: 152064 Hom.: 9667 Cov.: 32 AF XY: 0.338 AC XY: 25105 AN XY: 74340

Gnomad4 AFR AF: 0.479

Gnomad4 AMR AF: 0.256

Gnomad4 ASJ AF: 0.323

Gnomad4 EAS AF: 0.128

Gnomad4 SAS AF: 0.188

Gnomad4 FIN AF: 0.343

Gnomad4 NFE AF: 0.310

Gnomad4 OTH AF: 0.331

Alfa AF: 0.307 Hom.: 10880

Bravo AF: 0.343

Asia WGS AF: 0.165 AC: 574 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.6
DANN	Benign	0.78

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: rs1079199; hg19: chr11-6428106;