rs371350283
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_001130438.3(SPTAN1):c.237+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 0.0000967 in 1,613,832 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000072 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000099 ( 0 hom. )
Consequence
SPTAN1
NM_001130438.3 splice_donor_region, intron
NM_001130438.3 splice_donor_region, intron
Scores
2
Splicing: ADA: 0.00005021
2
Clinical Significance
Conservation
PhyloP100: -3.70
Genes affected
SPTAN1 (HGNC:11273): (spectrin alpha, non-erythrocytic 1) Spectrins are a family of filamentous cytoskeletal proteins that function as essential scaffold proteins that stabilize the plasma membrane and organize intracellular organelles. Spectrins are composed of alpha and beta dimers that associate to form tetramers linked in a head-to-head arrangement. This gene encodes an alpha spectrin that is specifically expressed in nonerythrocytic cells. The encoded protein has been implicated in other cellular functions including DNA repair and cell cycle regulation. Mutations in this gene are the cause of early infantile epileptic encephalopathy-5. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Sep 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.93).
BP6
?
Variant 9-128566981-C-T is Benign according to our data. Variant chr9-128566981-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 212295.We mark this variant Likely_benign, oryginal submissions are: {Benign=4, Uncertain_significance=1}.
BS2
?
High AC in GnomAd at 11 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SPTAN1 | NM_001130438.3 | c.237+4C>T | splice_donor_region_variant, intron_variant | ENST00000372739.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SPTAN1 | ENST00000372739.7 | c.237+4C>T | splice_donor_region_variant, intron_variant | 1 | NM_001130438.3 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000723 AC: 11AN: 152202Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000919 AC: 23AN: 250386Hom.: 0 AF XY: 0.0000958 AC XY: 13AN XY: 135682
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GnomAD4 exome AF: 0.0000992 AC: 145AN: 1461630Hom.: 0 Cov.: 31 AF XY: 0.0000935 AC XY: 68AN XY: 727130
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GnomAD4 genome ? AF: 0.0000723 AC: 11AN: 152202Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74358
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:4
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not specified Uncertain:1Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 09, 2015 | 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Nov 20, 2014 | - - |
Inborn genetic diseases Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | May 24, 2019 | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Early infantile epileptic encephalopathy with suppression bursts Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Oct 22, 2023 | - - |
Developmental and epileptic encephalopathy, 5 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 15, 2021 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Calibrated prediction
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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