rs1412243

Variant names:

• chr9-69532784-T-G
• rs1412243
• NM_001163.4:c.-69-15505A>C

Variant summary

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

The NM_001163.4(APBA1):​c.-69-15505A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 152,100 control chromosomes in the GnomAD database, including 4,165 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 (4165 hom., cov: 32)
• Consequence: APBA1 NM_001163.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.150
• Publications: 3 publications found

Genes affected

APBA1 (HGNC:578): (amyloid beta precursor protein binding family A member 1) The protein encoded by this gene is a member of the X11 protein family. It is a neuronal adapter protein that interacts with the Alzheimer's disease amyloid precursor protein (APP). It stabilizes APP and inhibits production of proteolytic APP fragments including the A beta peptide that is deposited in the brains of Alzheimer's disease patients. This gene product is believed to be involved in signal transduction processes. It is also regarded as a putative vesicular trafficking protein in the brain that can form a complex with the potential to couple synaptic vesicle exocytosis to neuronal cell adhesion. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.297 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APBA1	NM_001163.4	c.-69-15505A>C		intron_variant	Intron 1 of 12	ENST00000265381.7	NP_001154.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APBA1	ENST00000265381.7	c.-69-15505A>C		intron_variant	Intron 1 of 12	1	NM_001163.4	ENSP00000265381.3

Frequencies

GnomAD3 genomes AF: 0.229 AC: 34782 AN: 151982 Hom.: 4163 Cov.: 32

Gnomad AFR AF: 0.301

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.249

Gnomad ASJ AF: 0.187

Gnomad EAS AF: 0.213

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.232

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

GnomAD4 genome AF: 0.229 AC: 34814 AN: 152100 Hom.: 4165 Cov.: 32 AF XY: 0.225 AC XY: 16768 AN XY: 74374

African (AFR) AF: 0.301 AC: 12478 AN: 41448

American (AMR) AF: 0.249 AC: 3801 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.187 AC: 648 AN: 3472

East Asian (EAS) AF: 0.213 AC: 1102 AN: 5178

South Asian (SAS) AF: 0.179 AC: 861 AN: 4818

European-Finnish (FIN) AF: 0.149 AC: 1574 AN: 10590

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.202 AC: 13709 AN: 67996

Other (OTH) AF: 0.232 AC: 489 AN: 2108

Alfa AF: 0.213 Hom.: 10949

Bravo AF: 0.241

Asia WGS AF: 0.211 AC: 737 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.6
DANN	Benign	0.47
PhyloP100		0.15
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: rs1412243; hg19: chr9-72147700;