rs73399532
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_133642.5(LARGE1):c.1731-24T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00612 in 1,614,016 control chromosomes in the GnomAD database, including 496 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.033 ( 271 hom., cov: 32)
Exomes 𝑓: 0.0034 ( 225 hom. )
Consequence
LARGE1
NM_133642.5 intron
NM_133642.5 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.934
Genes affected
LARGE1 (HGNC:6511): (LARGE xylosyl- and glucuronyltransferase 1) This gene encodes a member of the N-acetylglucosaminyltransferase gene family. It encodes a glycosyltransferase which participates in glycosylation of alpha-dystroglycan, and may carry out the synthesis of glycoprotein and glycosphingolipid sugar chains. It may also be involved in the addition of a repeated disaccharide unit. The protein encoded by this gene is the glycotransferase that adds the final xylose and glucuronic acid to alpha-dystroglycan and thereby allows alpha-dystroglycan to bind ligands including laminin 211 and neurexin. Mutations in this gene cause several forms of congenital muscular dystrophy characterized by cognitive disability and abnormal glycosylation of alpha-dystroglycan. Alternative splicing of this gene results in multiple transcript variants that encode the same protein. [provided by RefSeq, May 2018]
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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=-0.79).
BP6
Variant 22-33283372-A-G is Benign according to our data. Variant chr22-33283372-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 95168.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-33283372-A-G is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LARGE1 | NM_133642.5 | c.1731-24T>C | intron_variant | ENST00000397394.8 | NP_598397.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LARGE1 | ENST00000397394.8 | c.1731-24T>C | intron_variant | 5 | NM_133642.5 | ENSP00000380549 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0325 AC: 4946AN: 152144Hom.: 270 Cov.: 32
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GnomAD3 exomes AF: 0.00871 AC: 2185AN: 250854Hom.: 95 AF XY: 0.00651 AC XY: 883AN XY: 135610
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GnomAD4 exome AF: 0.00337 AC: 4924AN: 1461754Hom.: 225 Cov.: 32 AF XY: 0.00290 AC XY: 2107AN XY: 727186
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GnomAD4 genome AF: 0.0325 AC: 4951AN: 152262Hom.: 271 Cov.: 32 AF XY: 0.0314 AC XY: 2336AN XY: 74456
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Likely benign, no assertion criteria provided | clinical testing | Genetic Services Laboratory, University of Chicago | - | - - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Nov 15, 2012 | - - |
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:2
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 30, 2018 | - - |
Computational scores
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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