9-69637353-G-A

Position:

• chr9-69637353-G-A

Variant summary

Our verdict is Benign. Variant got -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

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.376 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APBA1	NM_001163.4	c.-70+34800C>T		intron_variant		ENST00000265381.7
APBA1	XM_005251968.4	c.-70+34800C>T		intron_variant
APBA1	XM_011518617.3	c.-70+35498C>T		intron_variant
APBA1	XM_047423300.1	c.-2070+34800C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APBA1	ENST00000265381.7	c.-70+34800C>T		intron_variant		1	NM_001163.4	P1

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

Gnomad4 AFR AF: 0.381

Gnomad4 AMR AF: 0.221

Gnomad4 ASJ AF: 0.233

Gnomad4 EAS AF: 0.128

Gnomad4 SAS AF: 0.180

Gnomad4 FIN AF: 0.152

Gnomad4 NFE AF: 0.249

Gnomad4 OTH AF: 0.282

Alfa AF: 0.255 Hom.: 4769

Bravo AF: 0.278

Asia WGS AF: 0.190 AC: 662 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.41
DANN	Benign	0.38

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: rs10867845; hg19: chr9-72252269;