Variant chr11-6402596-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6BS2_Supporting

The NM_001164.5(APBB1):c.1234A>G(p.Met412Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000113 in 1,613,508 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00011 ( 1 hom. )

Consequence

APBB1
NM_001164.5 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.76

Variant links:

Genes affected

APBB1 (HGNC:581): (amyloid beta precursor protein binding family B member 1) The protein encoded by this gene is a member of the Fe65 protein family. It is an adaptor protein localized in the nucleus. It interacts with the Alzheimer's disease amyloid precursor protein (APP), transcription factor CP2/LSF/LBP1 and the low-density lipoprotein receptor-related protein. APP functions as a cytosolic anchoring site that can prevent the gene product's nuclear translocation. This encoded protein could play an important role in the pathogenesis of Alzheimer's disease. It is thought to regulate transcription. Also it is observed to block cell cycle progression by downregulating thymidylate synthase expression. Multiple alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Mar 2012]

APBB1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008874804).

BP6

Variant 11-6402596-T-C is Benign according to our data. Variant chr11-6402596-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3045487.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 24 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APBB1	NM_001164.5 linkuse as main transcript	c.1234A>G	p.Met412Val	missense_variant	7/15	ENST00000609360.6	NP_001155.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APBB1	ENST00000609360.6 linkuse as main transcript	c.1234A>G	p.Met412Val	missense_variant	7/15	5	NM_001164.5	ENSP00000477213	A1	O00213-1

Frequencies

GnomAD3 genomes

AF:

0.000158

AC:

AN:

151834

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000726

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00348

Gnomad SAS

AF:

0.000624

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000290

AC:

AN:

251416

Hom.:

AF XY:

0.000228

AC XY:

AN XY:

135884

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00348

Gnomad SAS exome

AF:

0.000229

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000109

AC:

159

AN:

1461558

Hom.:

Cov.:

AF XY:

0.000111

AC XY:

AN XY:

727124

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00310

Gnomad4 SAS exome

AF:

0.000243

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.000232

GnomAD4 genome

AF:

0.000158

AC:

AN:

151950

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74264

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00349

Gnomad4 SAS

AF:

0.000625

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000237

Hom.:

Bravo

AF:

0.000170

ExAC

AF:

0.000296

AC:

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

APBB1-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 31, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.056

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.0093

T;T;T;T;.;.;.;T;.;.;.;.;.;T

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.35

FATHMM_MKL

Benign

0.42

LIST_S2

Uncertain

0.91

D;.;D;D;D;.;.;D;D;.;D;D;D;D

M_CAP

Benign

0.0039

MetaRNN

Benign

0.0089

T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.34

.;.;.;.;.;.;N;N;N;.;.;.;.;.

MutationTaster

Benign

0.67

N;N;N;N;N

PrimateAI

Benign

0.42

PROVEAN

Benign

1.2

.;.;.;N;.;.;N;.;N;.;.;.;N;.

REVEL

Benign

0.13

Sift

Benign

1.0

.;.;.;T;.;.;T;.;T;.;.;.;T;.

Sift4G

Benign

1.0

T;T;T;T;T;T;T;T;T;T;T;T;T;.

Polyphen

0.0020

.;.;.;.;.;.;B;.;B;.;.;.;.;.

Vest4

0.25

MVP

0.41

MPC

0.32

ClinPred

0.013

GERP RS

3.4

Varity_R

0.28

gMVP

0.21

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over