rs1443187318

Variant names:

• chr7-44108060-T-TA
• rs1443187318
• NM_001129.5:c.917dupA

Variant summary

Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_001129.5(AEBP1):​c.917dupA​(p.Tyr306fs) variant causes a frameshift, stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000345 in 1,451,114 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. Y306Y) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: AEBP1 NM_001129.5 frameshift, stop_gained
• Clinical Significance: Pathogenic criteria provided, single submitter P:2
• Conservation: PhyloP100: 0.903
• 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: G2P, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp

ACMG classification

Our verdict: Pathogenic. The variant received 12 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 7-44108060-T-TA is Pathogenic according to our data. Variant chr7-44108060-T-TA is described in ClinVar as Pathogenic. ClinVar VariationId is 545699.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001129.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AEBP1	NM_001129.5	MANE Select	c.917dupA	p.Tyr306fs	frameshift stop_gained	Exon 6 of 21	NP_001120.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AEBP1	ENST00000223357.8	TSL:1 MANE Select	c.917dupA	p.Tyr306fs	frameshift stop_gained	Exon 6 of 21	ENSP00000223357.3	Q8IUX7-1
	AEBP1	ENST00000910440.1		c.929dupA	p.Tyr310fs	frameshift stop_gained	Exon 6 of 21	ENSP00000580499.1
	AEBP1	ENST00000910438.1		c.917dupA	p.Tyr306fs	frameshift stop_gained	Exon 6 of 21	ENSP00000580497.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.0000128 AC: 3 AN: 234350 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000287

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000345 AC: 5 AN: 1451114 Hom.: 0 Cov.: 35 AF XY: 0.00000139 AC XY: 1 AN XY: 720990

African (AFR) AF: 0.00 AC: 0 AN: 33188

American (AMR) AF: 0.00 AC: 0 AN: 43804

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25952

East Asian (EAS) AF: 0.00 AC: 0 AN: 39168

South Asian (SAS) AF: 0.00 AC: 0 AN: 84538

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51666

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4872

European-Non Finnish (NFE) AF: 0.00000451 AC: 5 AN: 1108018

Other (OTH) AF: 0.00 AC: 0 AN: 59908

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
2	-	-	Ehlers-Danlos syndrome, classic-like, 2 (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.90
Mutation Taster		=7/193	disease causing (ClinVar)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1443187318; hg19: chr7-44147659;