Variant 12-19440152-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_153207.5(AEBP2):c.453T>A(p.Asp151Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000239 in 1,497,930 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00025 ( 0 hom. )

Consequence

AEBP2
NM_153207.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.388

Variant links:

Genes affected

AEBP2 (HGNC:24051): (AE binding protein 2) Predicted to enable transcription coregulator activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to act upstream of or within regulation of transcription, DNA-templated. Located in nucleoplasm. Part of ESC/E(Z) complex. [provided by Alliance of Genome Resources, Apr 2022]

AEBP2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.013116628).

BS2

High AC in GnomAd4 at 24 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AEBP2	NM_153207.5 linkuse as main transcript	c.453T>A	p.Asp151Glu	missense_variant	1/8	ENST00000266508.14	NP_694939.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AEBP2	ENST00000266508.14 linkuse as main transcript	c.453T>A	p.Asp151Glu	missense_variant	1/8	1	NM_153207.5	ENSP00000266508		Q6ZN18-2
AEBP2	ENST00000398864.7 linkuse as main transcript	c.453T>A	p.Asp151Glu	missense_variant	1/9	1		ENSP00000381840	P1	Q6ZN18-1
AEBP2	ENST00000538425.5 linkuse as main transcript	c.-16-22358T>A		intron_variant		4		ENSP00000444255
AEBP2	ENST00000541908.5 linkuse as main transcript	c.-16-22358T>A		intron_variant		3		ENSP00000437983

Frequencies

GnomAD3 genomes

AF:

0.000163

AC:

AN:

147238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000253

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000673

Gnomad ASJ

AF:

0.00291

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000180

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000207

AC:

AN:

101318

Hom.:

AF XY:

0.000143

AC XY:

AN XY:

55802

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000471

Gnomad ASJ exome

AF:

0.00220

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000158

Gnomad OTH exome

AF:

0.000324

GnomAD4 exome

AF:

0.000247

AC:

334

AN:

1350692

Hom.:

Cov.:

AF XY:

0.000236

AC XY:

157

AN XY:

665370

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000614

Gnomad4 ASJ exome

AF:

0.00268

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000235

Gnomad4 OTH exome

AF:

0.000355

GnomAD4 genome

AF:

0.000163

AC:

AN:

147238

Hom.:

Cov.:

AF XY:

0.000195

AC XY:

AN XY:

71808

show subpopulations

Gnomad4 AFR

AF:

0.0000253

Gnomad4 AMR

AF:

0.0000673

Gnomad4 ASJ

AF:

0.00291

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000180

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000262

Hom.:

Bravo

AF:

0.000159

ExAC

AF:

0.0000908

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 03, 2022

The c.453T>A (p.D151E) alteration is located in exon 1 (coding exon 1) of the AEBP2 gene. This alteration results from a T to A substitution at nucleotide position 453, causing the aspartic acid (D) at amino acid position 151 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Uncertain

0.97

DEOGEN2

Benign

0.051

T;.

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.24

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.70

T;T

M_CAP

Pathogenic

0.84

MetaRNN

Benign

0.013

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.0

N;N

MutationTaster

Benign

1.0

D;N;N

PrimateAI

Pathogenic

0.95

PROVEAN

Benign

0.080

N;N

REVEL

Benign

0.064

Sift

Benign

0.041

D;D

Sift4G

Benign

0.79

T;T

Polyphen

0.12

B;.

Vest4

0.067

MutPred

0.16

Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);

MVP

0.14

MPC

1.0

ClinPred

0.046

GERP RS

4.0

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.6

Varity_R

0.18

gMVP

0.095

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