9-69485653-C-T

Position:

• chr9-69485653-C-T

Variant summary

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

The NM_001163.4(APBA1):​c.1201-9510G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.721 in 151,916 control chromosomes in the GnomAD database, including 39,822 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 0.72 (39822 hom., cov: 32)
• Consequence: APBA1 NM_001163.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.46

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.804 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APBA1	NM_001163.4	c.1201-9510G>A		intron_variant		ENST00000265381.7	NP_001154.2
LOC124902178	XR_007061570.1	n.91-8634C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APBA1	ENST00000265381.7	c.1201-9510G>A		intron_variant		1	NM_001163.4	ENSP00000265381	P1
	ENST00000429567.2	n.216-8634C>T		intron_variant, non_coding_transcript_variant		3
APBA1	ENST00000699288.1	c.46-9510G>A		intron_variant				ENSP00000514269

Frequencies

GnomAD3 genomes AF: 0.721 AC: 109403 AN: 151796 Hom.: 39779 Cov.: 32

Gnomad AFR AF: 0.672

Gnomad AMI AF: 0.882

Gnomad AMR AF: 0.787

Gnomad ASJ AF: 0.692

Gnomad EAS AF: 0.825

Gnomad SAS AF: 0.637

Gnomad FIN AF: 0.742

Gnomad MID AF: 0.682

Gnomad NFE AF: 0.730

Gnomad OTH AF: 0.717

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

GnomAD4 genome AF: 0.721 AC: 109506 AN: 151916 Hom.: 39822 Cov.: 32 AF XY: 0.720 AC XY: 53419 AN XY: 74212

Gnomad4 AFR AF: 0.672

Gnomad4 AMR AF: 0.787

Gnomad4 ASJ AF: 0.692

Gnomad4 EAS AF: 0.825

Gnomad4 SAS AF: 0.638

Gnomad4 FIN AF: 0.742

Gnomad4 NFE AF: 0.730

Gnomad4 OTH AF: 0.720

Alfa AF: 0.729 Hom.: 6611

Bravo AF: 0.725

Asia WGS AF: 0.760 AC: 2643 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.12
DANN	Benign	0.72

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: rs1331977; hg19: chr9-72100569;