chr7-44104702-C-T

Position:

chr7-44104702-C-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBS1_Supporting

The NM_001129.5(AEBP1):c.37C>T(p.Leu13Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000629 in 1,605,110 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000035 ( 1 hom. )

Consequence

AEBP1
NM_001129.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 0.847

Variant links:

Genes affected

AEBP1 (HGNC:303): (AE binding protein 1) This gene encodes a member of carboxypeptidase A protein family. The encoded protein may function as a transcriptional repressor and play a role in adipogenesis and smooth muscle cell differentiation. Studies in mice suggest that this gene functions in wound healing and abdominal wall development. Overexpression of this gene is associated with glioblastoma. [provided by RefSeq, May 2013]

AEBP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.037457526).

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000328 (50/152242) while in subpopulation AFR AF= 0.00118 (49/41570). AF 95% confidence interval is 0.000916. There are 0 homozygotes in gnomad4. There are 25 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AEBP1	NM_001129.5 linkuse as main transcript	c.37C>T	p.Leu13Phe	missense_variant	1/21	ENST00000223357.8	NP_001120.3	Q8IUX7-1
AEBP1	XM_011515162.2 linkuse as main transcript	c.37C>T	p.Leu13Phe	missense_variant	1/20		XP_011513464.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AEBP1	ENST00000223357.8 linkuse as main transcript	c.37C>T	p.Leu13Phe	missense_variant	1/21	1	NM_001129.5	ENSP00000223357.3		Q8IUX7-1

Frequencies

GnomAD3 genomes

AF:

0.000322

AC:

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00116

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000670

AC:

AN:

224010

Hom.:

AF XY:

0.0000727

AC XY:

AN XY:

123812

show subpopulations

Gnomad AFR exome

AF:

0.000971

Gnomad AMR exome

AF:

0.0000599

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000351

AC:

AN:

1452868

Hom.:

Cov.:

AF XY:

0.0000318

AC XY:

AN XY:

722160

show subpopulations

Gnomad4 AFR exome

AF:

0.00123

Gnomad4 AMR exome

AF:

0.0000453

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.000100

GnomAD4 genome

AF:

0.000328

AC:

AN:

152242

Hom.:

Cov.:

AF XY:

0.000336

AC XY:

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.00118

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000596

Hom.:

Bravo

AF:

0.000351

ExAC

AF:

0.0000838

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Uncertain:2

Uncertain significance, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Sep 24, 2021	This sequence change replaces leucine with phenylalanine at codon 13 of the AEBP1 protein (p.Leu13Phe). The leucine residue is weakly conserved and there is a small physicochemical difference between leucine and phenylalanine. This variant is present in population databases (rs545702407, ExAC 0.2%). This variant has not been reported in the literature in individuals affected with AEBP1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
Uncertain significance, criteria provided, single submitter	clinical testing	GeneDx	Jun 03, 2024	In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.11

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.077

Eigen

Uncertain

0.28

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Benign

0.60

LIST_S2

Benign

0.44

M_CAP

Pathogenic

0.66

MetaRNN

Benign

0.037

MetaSVM

Uncertain

0.75

MutationAssessor

Benign

0.97

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-0.39

REVEL

Uncertain

0.41

Sift

Pathogenic

0.0

Sift4G

Benign

0.33

Polyphen

1.0

Vest4

0.36

MutPred

0.25

Loss of stability (P = 0.2533);

MVP

0.72

MPC

0.92

ClinPred

0.097

GERP RS

3.9

Varity_R

0.15

gMVP

0.63

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