chr11-6412035-C-G

Variant names:

• chr11-6412035-C-G
• rs10839562
• NM_001164.5:c.-14-674G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001164.5(APBB1):​c.-14-674G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 152,204 control chromosomes in the GnomAD database, including 4,496 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 0.23 (4496 hom., cov: 33)
• Consequence: APBB1 NM_001164.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0860
• Publications: 3 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APBB1	NM_001164.5	c.-14-674G>C		intron_variant	Intron 1 of 14	ENST00000609360.6	NP_001155.1
APBB1	NM_145689.3	c.-14-674G>C		intron_variant	Intron 1 of 13		NP_663722.1
APBB1	NR_047512.2	n.128-674G>C		intron_variant	Intron 1 of 14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APBB1	ENST00000609360.6	c.-14-674G>C		intron_variant	Intron 1 of 14	5	NM_001164.5	ENSP00000477213.1

Frequencies

GnomAD3 genomes AF: 0.231 AC: 35076 AN: 152086 Hom.: 4496 Cov.: 33

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.205

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.303

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.312

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.296

Gnomad OTH AF: 0.243

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

GnomAD4 genome AF: 0.230 AC: 35077 AN: 152204 Hom.: 4496 Cov.: 33 AF XY: 0.228 AC XY: 16996 AN XY: 74402

African (AFR) AF: 0.124 AC: 5137 AN: 41540

American (AMR) AF: 0.212 AC: 3243 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.303 AC: 1051 AN: 3472

East Asian (EAS) AF: 0.113 AC: 585 AN: 5176

South Asian (SAS) AF: 0.171 AC: 826 AN: 4822

European-Finnish (FIN) AF: 0.312 AC: 3306 AN: 10582

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.296 AC: 20158 AN: 67996

Other (OTH) AF: 0.240 AC: 507 AN: 2110

Alfa AF: 0.264 Hom.: 758

Bravo AF: 0.217

Asia WGS AF: 0.125 AC: 435 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.6
DANN	Benign	0.62
PhyloP100		-0.086
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: rs10839562; hg19: chr11-6433265;