rs1042168
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_001114134.2(EPB42):c.330G>A(p.Ala110=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0077 in 1,614,172 control chromosomes in the GnomAD database, including 644 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.036 ( 336 hom., cov: 32)
Exomes 𝑓: 0.0047 ( 308 hom. )
Consequence
EPB42
NM_001114134.2 synonymous
NM_001114134.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.36
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 -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.74).
BP6
?
Variant 15-43215195-C-T is Benign according to our data. Variant chr15-43215195-C-T is described in ClinVar as [Benign]. Clinvar id is 255153.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-43215195-C-T is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=-1.36 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EPB42 | NM_001114134.2 | c.330G>A | p.Ala110= | synonymous_variant | 3/13 | ENST00000441366.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EPB42 | ENST00000441366.7 | c.330G>A | p.Ala110= | synonymous_variant | 3/13 | 1 | NM_001114134.2 | P1 | |
EPB42 | ENST00000648595.1 | c.420G>A | p.Ala140= | synonymous_variant | 3/13 | ||||
EPB42 | ENST00000540029.5 | c.196+1073G>A | intron_variant | 2 | |||||
EPB42 | ENST00000569204.1 | upstream_gene_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0363 AC: 5524AN: 152162Hom.: 334 Cov.: 32
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GnomAD3 exomes AF: 0.0121 AC: 3040AN: 251484Hom.: 144 AF XY: 0.00984 AC XY: 1338AN XY: 135912
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GnomAD4 exome AF: 0.00471 AC: 6887AN: 1461892Hom.: 308 Cov.: 32 AF XY: 0.00429 AC XY: 3122AN XY: 727246
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GnomAD4 genome ? AF: 0.0364 AC: 5543AN: 152280Hom.: 336 Cov.: 32 AF XY: 0.0344 AC XY: 2564AN XY: 74470
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ClinVar
Significance: Benign
Submissions summary: Benign:5
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 | Illumina Laboratory Services, Illumina | Jan 12, 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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 22, 2023 | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 11, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
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DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at