rs45498491
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001114134.2(EPB42):c.1318+4C>T variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0184 in 1,613,806 control chromosomes in the GnomAD database, including 326 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.015 ( 29 hom., cov: 32)
Exomes 𝑓: 0.019 ( 297 hom. )
Consequence
EPB42
NM_001114134.2 splice_donor_region, intron
NM_001114134.2 splice_donor_region, intron
Scores
2
Splicing: ADA: 0.00008317
2
Clinical Significance
Conservation
PhyloP100: -0.938
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.75).
BP6
?
Variant 15-43207195-G-A is Benign according to our data. Variant chr15-43207195-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 255149.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-43207195-G-A is described in Lovd as [Benign].
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0148 (2254/152236) while in subpopulation NFE AF= 0.0212 (1439/68000). AF 95% confidence interval is 0.0203. There are 29 homozygotes in gnomad4. There are 1041 alleles in male gnomad4 subpopulation. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 29 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EPB42 | NM_001114134.2 | c.1318+4C>T | splice_donor_region_variant, intron_variant | ENST00000441366.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EPB42 | ENST00000441366.7 | c.1318+4C>T | splice_donor_region_variant, intron_variant | 1 | NM_001114134.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0148 AC: 2255AN: 152118Hom.: 29 Cov.: 32
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GnomAD3 exomes AF: 0.0169 AC: 4222AN: 250552Hom.: 50 AF XY: 0.0165 AC XY: 2235AN XY: 135522
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GnomAD4 exome AF: 0.0188 AC: 27453AN: 1461570Hom.: 297 Cov.: 32 AF XY: 0.0184 AC XY: 13373AN XY: 727102
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GnomAD4 genome ? AF: 0.0148 AC: 2254AN: 152236Hom.: 29 Cov.: 32 AF XY: 0.0140 AC XY: 1041AN XY: 74452
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Hereditary spherocytosis type 5 Benign:2
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 29, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at