chr15-43206339-C-T
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_001114134.2(EPB42):c.1609G>A(p.Ala537Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00125 in 1,610,698 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001114134.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
EPB42 | ENST00000441366.7 | c.1609G>A | p.Ala537Thr | missense_variant | Exon 10 of 13 | 1 | NM_001114134.2 | ENSP00000396616.2 | ||
ENSG00000285117 | ENST00000563128.5 | n.143G>A | non_coding_transcript_exon_variant | Exon 1 of 4 | 3 | ENSP00000520455.1 |
Frequencies
GnomAD3 genomes AF: 0.00104 AC: 158AN: 152124Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00107 AC: 267AN: 248638Hom.: 0 AF XY: 0.00104 AC XY: 140AN XY: 134506
GnomAD4 exome AF: 0.00128 AC: 1862AN: 1458456Hom.: 6 Cov.: 32 AF XY: 0.00131 AC XY: 947AN XY: 724856
GnomAD4 genome AF: 0.00104 AC: 158AN: 152242Hom.: 0 Cov.: 32 AF XY: 0.000887 AC XY: 66AN XY: 74432
ClinVar
Submissions by phenotype
Hereditary spherocytosis type 5 Uncertain:2
The EPB42 c.1699G>A; p.Ala567Thr variant (rs45495503, ClinVar variation ID: 132637), is reported in the literature in one individual affected with hemolytic anemia and alpha thalassemia, this individual also carried a splice donor variant in EPB42 and two copies of the 3.7kb alpha globin deletion (Maciag 2009). This variant is found in the general population with an overall allele frequency of 0.1% (303/279,988 alleles) in the Genome Aggregation Database. Computational analyses predict that this variant is neutral (REVEL: 0.105). Due to limited information, the clinical significance of this EPB42 variant is uncertain at this time. References: Maciag M et al. The use of real-time PCR technique in the detection of novel protein 4.2 gene mutations that coexist with thalassaemia alpha in a single patient. Eur J Haematol. 2009 Oct. PMID: 19508687 -
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not provided Uncertain:1Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at