rs11139519

Positions:

• chr9-69621565-G-A
• chr9-69621565-G-T

Variant summary

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

The NM_001163.4(APBA1):​c.-70+50588C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 152,080 control chromosomes in the GnomAD database, including 1,654 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 0.13 (1654 hom., cov: 33)
• Consequence: APBA1 NM_001163.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.31

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.234 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APBA1	NM_001163.4	c.-70+50588C>T		intron_variant		ENST00000265381.7	NP_001154.2
APBA1	XM_011518617.3	c.-70+51286C>T		intron_variant			XP_011516919.1
APBA1	XM_047423300.1	c.-2069-50483C>T		intron_variant			XP_047279256.1
APBA1	XM_005251968.4	c.-70+50588C>T		intron_variant			XP_005252025.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APBA1	ENST00000265381.7	c.-70+50588C>T		intron_variant		1	NM_001163.4	ENSP00000265381.3

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19620 AN: 151960 Hom.: 1643 Cov.: 33

Gnomad AFR AF: 0.0384

Gnomad AMI AF: 0.229

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.245

Gnomad SAS AF: 0.0677

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.142

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

GnomAD4 genome AF: 0.129 AC: 19644 AN: 152080 Hom.: 1654 Cov.: 33 AF XY: 0.127 AC XY: 9454 AN XY: 74326

Gnomad4 AFR AF: 0.0383

Gnomad4 AMR AF: 0.217

Gnomad4 ASJ AF: 0.107

Gnomad4 EAS AF: 0.245

Gnomad4 SAS AF: 0.0684

Gnomad4 FIN AF: 0.109

Gnomad4 NFE AF: 0.162

Gnomad4 OTH AF: 0.147

Alfa AF: 0.151 Hom.: 1491

Bravo AF: 0.137

Asia WGS AF: 0.178 AC: 617 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	10
DANN	Benign	0.74

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

Publications

LitVar

Other links and lift over

dbSNP: rs11139519; hg19: chr9-72236481;