Variant 7-44104667-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PVS1_SupportingPM2PP5_Moderate

The NM_001129.5(AEBP1):c.2T>A(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000743 in 1,345,482 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.4e-7 ( 0 hom. )

Consequence

AEBP1
NM_001129.5 start_lost

Scores

Clinical Significance

Likely pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 2.22

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 Uncertain_significance. Variant got 5 ACMG points.

PVS1

Start lost variant, no pathogenic variants between lost start and next in-frame start position. Next in-frame start position is after 314 codons. Genomic position: 44108084. Lost 0.270 part of the original CDS.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 7-44104667-T-A is Pathogenic according to our data. Variant chr7-44104667-T-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 1012796.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AEBP1	NM_001129.5 link	c.2T>A	p.Met1?	start_lost	Exon 1 of 21	ENST00000223357.8	NP_001120.3	Q8IUX7-1
AEBP1	XM_011515162.2 link	c.2T>A	p.Met1?	start_lost	Exon 1 of 20		XP_011513464.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AEBP1	ENST00000223357.8 link	c.2T>A	p.Met1?	start_lost	Exon 1 of 21	1	NM_001129.5	ENSP00000223357.3		Q8IUX7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000880

AC:

AN:

113630

Hom.:

AF XY:

0.0000155

AC XY:

AN XY:

64562

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000559

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.43e-7

AC:

AN:

1345482

Hom.:

Cov.:

AF XY:

0.00000151

AC XY:

AN XY:

663294

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000137

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000927

AC:

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Pathogenic:1

Nov 01, 2020

CeGaT Center for Human Genetics Tuebingen

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Uncertain

0.16

BayesDel_noAF

Pathogenic

0.15

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.044

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.38

FATHMM_MKL

Benign

0.18

LIST_S2

Uncertain

0.90

M_CAP

Pathogenic

0.98

MetaRNN

Pathogenic

0.98

MetaSVM

Uncertain

0.054

PROVEAN

Benign

-0.20

REVEL

Uncertain

0.55

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.65

Vest4

0.85

MutPred

0.92

Loss of stability (P = 0.0461);

MVP

0.47

ClinPred

0.46

GERP RS

1.5

Varity_R

0.76

gMVP

0.75

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