8-143922240-T-G
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_201384.3(PLEC):c.7581A>C(p.Ala2527Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.387 in 1,585,694 control chromosomes in the GnomAD database, including 125,267 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
NM_201384.3 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -21 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PLEC | ENST00000345136.8 | c.7581A>C | p.Ala2527Ala | synonymous_variant | Exon 32 of 32 | 1 | NM_201384.3 | ENSP00000344848.3 | ||
PLEC | ENST00000356346.7 | c.7539A>C | p.Ala2513Ala | synonymous_variant | Exon 32 of 32 | 1 | NM_201378.4 | ENSP00000348702.3 |
Frequencies
GnomAD3 genomes AF: 0.303 AC: 46018AN: 152114Hom.: 8648 Cov.: 34
GnomAD3 exomes AF: 0.336 AC: 69370AN: 206604Hom.: 12846 AF XY: 0.347 AC XY: 39381AN XY: 113380
GnomAD4 exome AF: 0.396 AC: 568035AN: 1433462Hom.: 116620 Cov.: 80 AF XY: 0.396 AC XY: 281806AN XY: 711860
GnomAD4 genome AF: 0.302 AC: 45996AN: 152232Hom.: 8647 Cov.: 34 AF XY: 0.302 AC XY: 22451AN XY: 74428
ClinVar
Submissions by phenotype
not specified Benign:5
Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -
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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. -
p.Ala2664Ala in exon 32 of PLEC: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue and is not located w ithin the splice consensus sequence. It has been identified in 40.1% (3440/8572) of European American chromosomes from a broad population by the NHLBI Exome Seq uencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs11778026). -
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Epidermolysis bullosa simplex with nail dystrophy Benign:1
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Epidermolysis bullosa simplex, Ogna type;C2677349:Epidermolysis bullosa simplex 5C, with pyloric atresia;C2931072:Epidermolysis bullosa simplex 5B, with muscular dystrophy;C3150989:Autosomal recessive limb-girdle muscular dystrophy type 2Q;C4225309:Epidermolysis bullosa simplex with nail dystrophy Benign:1
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Epidermolysis bullosa simplex 5C, with pyloric atresia Benign:1
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Epidermolysis bullosa simplex 5B, with muscular dystrophy Benign:1
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not provided Benign:1
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Autosomal recessive limb-girdle muscular dystrophy type 2Q Benign:1
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Epidermolysis bullosa simplex, Ogna type Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at