rs140429638
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2
The NM_018100.4(EFHC1):c.90G>A(p.Thr30=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000643 in 1,613,892 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00057 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00065 ( 1 hom. )
Consequence
EFHC1
NM_018100.4 synonymous
NM_018100.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -3.05
Genes affected
EFHC1 (HGNC:16406): (EF-hand domain containing 1) This gene encodes an EF-hand-containing calcium binding protein. The encoded protein likely plays a role in calcium homeostasis. Mutations in this gene have been associated with susceptibility to juvenile myoclonic epilepsy and juvenile absence epilepsy. Alternatively spliced transcript variants have been described. [provided by RefSeq, Feb 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.74).
BP6
?
Variant 6-52423972-G-A is Benign according to our data. Variant chr6-52423972-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 128971.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=2, Benign=1, Likely_benign=1}.
BP7
?
Synonymous conserved (PhyloP=-3.05 with no splicing effect.
BS2
?
High AC in GnomAd4 at 87 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EFHC1 | NM_018100.4 | c.90G>A | p.Thr30= | synonymous_variant | 2/11 | ENST00000371068.11 | |
EFHC1 | NM_001172420.2 | c.33G>A | p.Thr11= | synonymous_variant | 3/12 | ||
EFHC1 | NR_033327.2 | n.159G>A | non_coding_transcript_exon_variant | 2/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EFHC1 | ENST00000371068.11 | c.90G>A | p.Thr30= | synonymous_variant | 2/11 | 1 | NM_018100.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000573 AC: 87AN: 151902Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000422 AC: 106AN: 251402Hom.: 0 AF XY: 0.000464 AC XY: 63AN XY: 135890
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GnomAD4 exome AF: 0.000650 AC: 950AN: 1461872Hom.: 1 Cov.: 33 AF XY: 0.000594 AC XY: 432AN XY: 727244
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GnomAD4 genome ? AF: 0.000572 AC: 87AN: 152020Hom.: 0 Cov.: 32 AF XY: 0.000619 AC XY: 46AN XY: 74300
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Juvenile myoclonic epilepsy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Nov 26, 2013 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 19, 2013 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Absence seizure;C1850778:Myoclonic epilepsy, juvenile, susceptibility to, 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 11, 2023 | - - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
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