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GeneBe

15-29054265-C-T

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_001353788.2(APBA2):c.381C>T(p.His127=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00744 in 1,614,142 control chromosomes in the GnomAD database, including 65 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0074 ( 12 hom., cov: 33)
Exomes 𝑓: 0.0074 ( 53 hom. )

Consequence

APBA2
NM_001353788.2 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.506
Variant links:
Genes affected
APBA2 (HGNC:579): (amyloid beta precursor protein binding family A member 2) 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 2017]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 15-29054265-C-T is Benign according to our data. Variant chr15-29054265-C-T is described in ClinVar as [Benign]. Clinvar id is 770621.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.506 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 12 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
APBA2NM_001353788.2 linkuse as main transcriptc.381C>T p.His127= synonymous_variant 4/15 ENST00000683413.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
APBA2ENST00000683413.1 linkuse as main transcriptc.381C>T p.His127= synonymous_variant 4/15 NM_001353788.2 P1Q99767-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00740
AC:
1126
AN:
152166
Hom.:
12
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00166
Gnomad AMI
AF:
0.0965
Gnomad AMR
AF:
0.0166
Gnomad ASJ
AF:
0.0141
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00352
Gnomad FIN
AF:
0.00141
Gnomad MID
AF:
0.0127
Gnomad NFE
AF:
0.00886
Gnomad OTH
AF:
0.0129
GnomAD3 exomes
AF:
0.00705
AC:
1772
AN:
251218
Hom.:
11
AF XY:
0.00744
AC XY:
1011
AN XY:
135812
show subpopulations
Gnomad AFR exome
AF:
0.00123
Gnomad AMR exome
AF:
0.0108
Gnomad ASJ exome
AF:
0.0166
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00447
Gnomad FIN exome
AF:
0.00129
Gnomad NFE exome
AF:
0.00859
Gnomad OTH exome
AF:
0.0118
GnomAD4 exome
AF:
0.00744
AC:
10878
AN:
1461858
Hom.:
53
Cov.:
32
AF XY:
0.00753
AC XY:
5476
AN XY:
727224
show subpopulations
Gnomad4 AFR exome
AF:
0.00143
Gnomad4 AMR exome
AF:
0.0113
Gnomad4 ASJ exome
AF:
0.0153
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00434
Gnomad4 FIN exome
AF:
0.00142
Gnomad4 NFE exome
AF:
0.00804
Gnomad4 OTH exome
AF:
0.00806
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00739
AC:
1125
AN:
152284
Hom.:
12
Cov.:
33
AF XY:
0.00731
AC XY:
544
AN XY:
74446
show subpopulations
Gnomad4 AFR
AF:
0.00166
Gnomad4 AMR
AF:
0.0166
Gnomad4 ASJ
AF:
0.0141
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00352
Gnomad4 FIN
AF:
0.00141
Gnomad4 NFE
AF:
0.00887
Gnomad4 OTH
AF:
0.0128
Alfa
AF:
0.00748
Hom.:
1
Bravo
AF:
0.00851
Asia WGS
AF:
0.00346
AC:
12
AN:
3478
EpiCase
AF:
0.0106
EpiControl
AF:
0.0124

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

APBA2-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesFeb 21, 2019This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.83
Cadd
Benign
0.41
Dann
Benign
0.48
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.8

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs137995892; hg19: chr15-29346468; API