Variant 12-19440005-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000266508.14(AEBP2):c.306C>G(p.Asp102Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000101 in 1,519,714 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another nucleotide change resulting in same amino acid change has been previously reported as Uncertain significancein ClinVar.

Frequency

Genomes: 𝑓 0.00025 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000085 ( 0 hom. )

Consequence

AEBP2
ENST00000266508.14 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.385

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=0.0059719086).

BS2

High AC in GnomAd4 at 37 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AEBP2	NM_153207.5 linkuse as main transcript	c.306C>G	p.Asp102Glu	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.306C>G	p.Asp102Glu	missense_variant	1/8	1	NM_153207.5	ENSP00000266508		Q6ZN18-2
AEBP2	ENST00000398864.7 linkuse as main transcript	c.306C>G	p.Asp102Glu	missense_variant	1/9	1		ENSP00000381840	P1	Q6ZN18-1
AEBP2	ENST00000538425.5 linkuse as main transcript	c.-16-22505C>G		intron_variant		4		ENSP00000444255
AEBP2	ENST00000541908.5 linkuse as main transcript	c.-16-22505C>G		intron_variant		3		ENSP00000437983

Frequencies

GnomAD3 genomes

AF:

0.000246

AC:

AN:

150174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000246

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00126

Gnomad ASJ

AF:

0.00347

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000741

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000271

AC:

AN:

121902

Hom.:

AF XY:

0.000226

AC XY:

AN XY:

66400

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000426

Gnomad ASJ exome

AF:

0.00371

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000420

Gnomad OTH exome

AF:

0.000541

GnomAD4 exome

AF:

0.0000854

AC:

117

AN:

1369426

Hom.:

Cov.:

AF XY:

0.0000843

AC XY:

AN XY:

675996

show subpopulations

Gnomad4 AFR exome

AF:

0.0000701

Gnomad4 AMR exome

AF:

0.0000868

Gnomad4 ASJ exome

AF:

0.00343

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000140

Gnomad4 OTH exome

AF:

0.000227

GnomAD4 genome

AF:

0.000246

AC:

AN:

150288

Hom.:

Cov.:

AF XY:

0.000300

AC XY:

AN XY:

73362

show subpopulations

Gnomad4 AFR

AF:

0.0000245

Gnomad4 AMR

AF:

0.00125

Gnomad4 ASJ

AF:

0.00347

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000741

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000360

Hom.:

Bravo

AF:

0.000348

ExAC

AF:

0.000106

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

Apr 07, 2022

The c.306C>G (p.D102E) alteration is located in exon 1 (coding exon 1) of the AEBP2 gene. This alteration results from a C to G substitution at nucleotide position 306, causing the aspartic acid (D) at amino acid position 102 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

0.064

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.57

CADD

Benign

2.6

DANN

Benign

0.78

DEOGEN2

Benign

0.056

T;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.037

LIST_S2

Benign

0.37

T;T

M_CAP

Pathogenic

0.81

MetaRNN

Benign

0.0060

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;N

MutationTaster

Benign

1.0

D;N;N

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-0.58

N;N

REVEL

Benign

0.065

Sift

Benign

0.26

T;T

Sift4G

Benign

0.75

T;T

Polyphen

0.0

B;.

Vest4

0.080

MutPred

0.12

Gain of helix (P = 0.0496);Gain of helix (P = 0.0496);

MVP

0.10

MPC

1.0

ClinPred

0.021

GERP RS

-0.51

Varity_R

0.055

gMVP

0.015

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