chr7-44110261-GCCAGGAC-G

Variant names:

• chr7-44110261-GCCAGGAC-G
• rs1554327284
• NM_001129.5:c.1320_1326delGACCCAG

Variant summary

Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_001129.5(AEBP1):​c.1320_1326delGACCCAG​(p.Arg440SerfsTer3) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 33)
• Consequence: AEBP1 NM_001129.5 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 3.05
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• Ehlers-Danlos syndrome, classic-like, 2

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet, Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia, Ambry Genetics

ACMG classification

Our verdict: Pathogenic. The variant received 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 7-44110261-GCCAGGAC-G is Pathogenic according to our data. Variant chr7-44110261-GCCAGGAC-G is described in ClinVar as Pathogenic. ClinVar VariationId is 545024.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AEBP1	NM_001129.5	c.1320_1326delGACCCAG	p.Arg440SerfsTer3	frameshift_variant	Exon 11 of 21	ENST00000223357.8	NP_001120.3
AEBP1	XM_011515162.2	c.1242_1248delGACCCAG	p.Arg414SerfsTer3	frameshift_variant	Exon 10 of 20		XP_011513464.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AEBP1	ENST00000223357.8	c.1320_1326delGACCCAG	p.Arg440SerfsTer3	frameshift_variant	Exon 11 of 21	1	NM_001129.5	ENSP00000223357.3

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Ehlers-Danlos syndrome, classic-like, 2 Pathogenic:1

May 30, 2018

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.1
Mutation Taster		=26/174	disease causing (ClinVar)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1554327284; hg19: chr7-44149860;