rs74709220
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_182961.4(SYNE1):c.24977-1678T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0152 in 1,571,464 control chromosomes in the GnomAD database, including 1,367 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.012 ( 106 hom., cov: 32)
Exomes 𝑓: 0.016 ( 1261 hom. )
Consequence
SYNE1
NM_182961.4 intron
NM_182961.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.00
Genes affected
SYNE1 (HGNC:17089): (spectrin repeat containing nuclear envelope protein 1) This gene encodes a spectrin repeat containing protein expressed in skeletal and smooth muscle, and peripheral blood lymphocytes, that localizes to the nuclear membrane. Mutations in this gene have been associated with autosomal recessive spinocerebellar ataxia 8, also referred to as autosomal recessive cerebellar ataxia type 1 or recessive ataxia of Beauce. Alternatively spliced transcript variants encoding different isoforms have been described. [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=-0.81).
BP6
?
Variant 6-152145443-A-C is Benign according to our data. Variant chr6-152145443-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 262191.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.127 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SYNE1 | NM_001347702.2 | c.1510+44T>G | intron_variant | ENST00000354674.5 | |||
SYNE1 | NM_182961.4 | c.24977-1678T>G | intron_variant | ENST00000367255.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SYNE1 | ENST00000354674.5 | c.1510+44T>G | intron_variant | 5 | NM_001347702.2 | ||||
SYNE1 | ENST00000367255.10 | c.24977-1678T>G | intron_variant | 1 | NM_182961.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0125 AC: 1907AN: 152128Hom.: 107 Cov.: 32
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GnomAD3 exomes AF: 0.0300 AC: 7473AN: 249170Hom.: 462 AF XY: 0.0352 AC XY: 4745AN XY: 134672
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GnomAD4 exome AF: 0.0155 AC: 22016AN: 1419218Hom.: 1261 Cov.: 23 AF XY: 0.0193 AC XY: 13709AN XY: 708654
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GnomAD4 genome ? AF: 0.0125 AC: 1902AN: 152246Hom.: 106 Cov.: 32 AF XY: 0.0147 AC XY: 1094AN XY: 74448
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 28, 2018 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at