rs376218204
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_182961.4(SYNE1):c.5421+9G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0002 in 1,563,100 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
Consequence
NM_182961.4 intron
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SYNE1 | NM_182961.4 | c.5421+9G>T | intron_variant | Intron 40 of 145 | ENST00000367255.10 | NP_892006.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SYNE1 | ENST00000367255.10 | c.5421+9G>T | intron_variant | Intron 40 of 145 | 1 | NM_182961.4 | ENSP00000356224.5 | |||
SYNE1 | ENST00000423061.6 | c.5442+9G>T | intron_variant | Intron 40 of 145 | 1 | ENSP00000396024.1 | ||||
SYNE1 | ENST00000461872.6 | n.5639+9G>T | intron_variant | Intron 38 of 54 | 1 |
Frequencies
GnomAD3 genomes AF: 0.000573 AC: 81AN: 141286Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000263 AC: 61AN: 231670Hom.: 0 AF XY: 0.000224 AC XY: 28AN XY: 125272
GnomAD4 exome AF: 0.000162 AC: 230AN: 1421764Hom.: 0 Cov.: 33 AF XY: 0.000153 AC XY: 108AN XY: 706344
GnomAD4 genome AF: 0.000580 AC: 82AN: 141336Hom.: 0 Cov.: 32 AF XY: 0.000481 AC XY: 33AN XY: 68654
ClinVar
Submissions by phenotype
not specified Uncertain:1Benign:1
- -
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. -
not provided Uncertain:1
- -
Autosomal recessive ataxia, Beauce type Uncertain:1
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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -
Autosomal recessive ataxia, Beauce type;C2751807:Emery-Dreifuss muscular dystrophy 4, autosomal dominant Benign:1
- -
Emery-Dreifuss muscular dystrophy 4, autosomal dominant Benign:1
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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at