9-69637353-G-A

Variant names:

• chr9-69637353-G-A
• rs10867845
• NM_001163.4:c.-70+34800C>T

Variant summary

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

The NM_001163.4(APBA1):​c.-70+34800C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 151,974 control chromosomes in the GnomAD database, including 5,961 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 0.27 (5961 hom., cov: 32)
• Consequence: APBA1 NM_001163.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.539
• Publications: 4 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.376 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001163.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APBA1	NM_001163.4	MANE Select	c.-70+34800C>T		intron	N/A	NP_001154.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APBA1	ENST00000265381.7	TSL:1 MANE Select	c.-70+34800C>T		intron	N/A	ENSP00000265381.3

Frequencies

GnomAD3 genomes AF: 0.268 AC: 40712 AN: 151854 Hom.: 5943 Cov.: 32

Gnomad AFR AF: 0.381

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.221

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.128

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.249

Gnomad OTH AF: 0.281

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

GnomAD4 genome AF: 0.268 AC: 40777 AN: 151974 Hom.: 5961 Cov.: 32 AF XY: 0.261 AC XY: 19400 AN XY: 74314

African (AFR) AF: 0.381 AC: 15786 AN: 41398

American (AMR) AF: 0.221 AC: 3370 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.233 AC: 808 AN: 3472

East Asian (EAS) AF: 0.128 AC: 661 AN: 5182

South Asian (SAS) AF: 0.180 AC: 865 AN: 4812

European-Finnish (FIN) AF: 0.152 AC: 1604 AN: 10578

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.249 AC: 16896 AN: 67940

Other (OTH) AF: 0.282 AC: 594 AN: 2110

Alfa AF: 0.257 Hom.: 5892

Bravo AF: 0.278

Asia WGS AF: 0.190 AC: 662 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.41
DANN	Benign	0.38
PhyloP100		-0.54
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: rs10867845; hg19: chr9-72252269;