rs869025285
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PVS1PP5
The NM_001376013.1(EPB41):c.1071_1077del(p.Asn358ProfsTer18) variant causes a frameshift change involving the alteration of a conserved nucleotide. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Consequence
EPB41
NM_001376013.1 frameshift
NM_001376013.1 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 9.25
Genes affected
EPB41 (HGNC:3377): (erythrocyte membrane protein band 4.1) The protein encoded by this gene, together with spectrin and actin, constitute the red cell membrane cytoskeletal network. This complex plays a critical role in erythrocyte shape and deformability. Mutations in this gene are associated with type 1 elliptocytosis (EL1). Alternatively spliced transcript variants encoding different isoforms have been described for this gene.[provided by RefSeq, Oct 2009]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 9 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PP5
?
Variant 1-29018388-CGAATCAG-C is Pathogenic according to our data. Variant chr1-29018388-CGAATCAG-C is described in ClinVar as [Pathogenic]. Clinvar id is 221297.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EPB41 | NM_001376013.1 | c.1071_1077del | p.Asn358ProfsTer18 | frameshift_variant | 7/21 | ENST00000343067.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EPB41 | ENST00000343067.9 | c.1071_1077del | p.Asn358ProfsTer18 | frameshift_variant | 7/21 | 5 | NM_001376013.1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Hereditary elliptocytosis Pathogenic:1
Pathogenic, no assertion criteria provided | clinical testing | Sankaran Lab, Boston Children's Hospital | Dec 25, 2015 | Homozygous loss of function in EPB41, similar to 3 prior cases in literature - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at