rs266257354
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_001114134.2(EPB42):c.175delG(p.Val59TrpfsTer48) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,614,002 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. V59V) has been classified as Uncertain significance. Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
EPB42
NM_001114134.2 frameshift
NM_001114134.2 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.123
Publications
1 publications found
Genes affected
EPB42 (HGNC:3381): (erythrocyte membrane protein band 4.2) Erythrocyte membrane protein band 4.2 is an ATP-binding protein which may regulate the association of protein 3 with ankyrin. It probably has a role in erythrocyte shape and mechanical property regulation. Mutations in the EPB42 gene are associated with recessive spherocytic elliptocytosis and recessively transmitted hereditary hemolytic anemia. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
EPB42 Gene-Disease associations (from GenCC):
- hereditary spherocytosis type 5Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
- hereditary spherocytosisInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
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 15-43216288-AC-A is Pathogenic according to our data. Variant chr15-43216288-AC-A is described in ClinVar as Pathogenic. ClinVar VariationId is 13234.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| EPB42 | NM_001114134.2 | c.175delG | p.Val59TrpfsTer48 | frameshift_variant | Exon 2 of 13 | ENST00000441366.7 | NP_001107606.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| EPB42 | ENST00000441366.7 | c.175delG | p.Val59TrpfsTer48 | frameshift_variant | Exon 2 of 13 | 1 | NM_001114134.2 | ENSP00000396616.2 | ||
| EPB42 | ENST00000648595.1 | c.265delG | p.Val89TrpfsTer48 | frameshift_variant | Exon 2 of 13 | ENSP00000497777.1 | ||||
| EPB42 | ENST00000540029.5 | c.175delG | p.Val59TrpfsTer13 | frameshift_variant | Exon 2 of 12 | 2 | ENSP00000444699.1 |
Frequencies
GnomAD3 genomes 0.00000657 AC: 1AN: 152224Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
152224
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461778Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727184 show subpopulations
GnomAD4 exome
AF:
AC:
2
AN:
1461778
Hom.:
Cov.:
31
AF XY:
AC XY:
1
AN XY:
727184
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33478
American (AMR)
AF:
AC:
1
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26136
East Asian (EAS)
AF:
AC:
0
AN:
39700
South Asian (SAS)
AF:
AC:
0
AN:
86252
European-Finnish (FIN)
AF:
AC:
0
AN:
53406
Middle Eastern (MID)
AF:
AC:
0
AN:
5680
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1112012
Other (OTH)
AF:
AC:
0
AN:
60390
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.550
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
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10
<30
30-35
35-40
40-45
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>80
Age
GnomAD4 genome 0.00000657 AC: 1AN: 152224Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74378 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
152224
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
74378
show subpopulations
African (AFR)
AF:
AC:
1
AN:
41452
American (AMR)
AF:
AC:
0
AN:
15288
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3466
East Asian (EAS)
AF:
AC:
0
AN:
5202
South Asian (SAS)
AF:
AC:
0
AN:
4832
European-Finnish (FIN)
AF:
AC:
0
AN:
10628
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
0
AN:
68034
Other (OTH)
AF:
AC:
0
AN:
2094
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Hereditary spherocytosis type 5 Pathogenic:1
Jan 01, 1995
OMIM
Significance:Pathogenic
Review Status:no assertion criteria provided
Collection Method:literature only
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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