8-143916158-G-A
Variant names:
Variant summary
Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_201384.3(PLEC):c.*19C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00859 in 1,521,982 control chromosomes in the GnomAD database, including 1,022 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.045 ( 543 hom., cov: 34)
Exomes 𝑓: 0.0045 ( 479 hom. )
Consequence
PLEC
NM_201384.3 3_prime_UTR
NM_201384.3 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.771
Genes affected
PLEC (HGNC:9069): (plectin) Plectin is a prominent member of an important family of structurally and in part functionally related proteins, termed plakins or cytolinkers, that are capable of interlinking different elements of the cytoskeleton. Plakins, with their multi-domain structure and enormous size, not only play crucial roles in maintaining cell and tissue integrity and orchestrating dynamic changes in cytoarchitecture and cell shape, but also serve as scaffolding platforms for the assembly, positioning, and regulation of signaling complexes (reviewed in PMID: 9701547, 11854008, and 17499243). Plectin is expressed as several protein isoforms in a wide range of cell types and tissues from a single gene located on chromosome 8 in humans (PMID: 8633055, 8698233). Until 2010, this locus was named plectin 1 (symbol PLEC1 in human; Plec1 in mouse and rat) and the gene product had been referred to as "hemidesmosomal protein 1" or "plectin 1, intermediate filament binding 500kDa". These names were superseded by plectin. The plectin gene locus in mouse on chromosome 15 has been analyzed in detail (PMID: 10556294, 14559777), revealing a genomic exon-intron organization with well over 40 exons spanning over 62 kb and an unusual 5' transcript complexity of plectin isoforms. Eleven exons (1-1j) have been identified that alternatively splice directly into a common exon 2 which is the first exon to encode plectin's highly conserved actin binding domain (ABD). Three additional exons (-1, 0a, and 0) splice into an alternative first coding exon (1c), and two additional exons (2alpha and 3alpha) are optionally spliced within the exons encoding the acting binding domain (exons 2-8). Analysis of the human locus has identified eight of the eleven alternative 5' exons found in mouse and rat (PMID: 14672974); exons 1i, 1j and 1h have not been confirmed in human. Furthermore, isoforms lacking the central rod domain encoded by exon 31 have been detected in mouse (PMID:10556294), rat (PMID: 9177781), and human (PMID: 11441066, 10780662, 20052759). The short alternative amino-terminal sequences encoded by the different first exons direct the targeting of the various isoforms to distinct subcellular locations (PMID: 14559777). As the expression of specific plectin isoforms was found to be dependent on cell type (tissue) and stage of development (PMID: 10556294, 12542521, 17389230) it appears that each cell type (tissue) contains a unique set (proportion and composition) of plectin isoforms, as if custom-made for specific requirements of the particular cells. Concordantly, individual isoforms were found to carry out distinct and specific functions (PMID: 14559777, 12542521, 18541706). In 1996, a number of groups reported that patients suffering from epidermolysis bullosa simplex with muscular dystrophy (EBS-MD) lacked plectin expression in skin and muscle tissues due to defects in the plectin gene (PMID: 8698233, 8941634, 8636409, 8894687, 8696340). Two other subtypes of plectin-related EBS have been described: EBS-pyloric atresia (PA) and EBS-Ogna. For reviews of plectin-related diseases see PMID: 15810881, 19945614. Mutations in the plectin gene related to human diseases should be named based on the position in NM_000445 (variant 1, isoform 1c), unless the mutation is located within one of the other alternative first exons, in which case the position in the respective Reference Sequence should be used. [provided by RefSeq, Aug 2011]
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Benign. The variant received -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.74).
BP6
Variant 8-143916158-G-A is Benign according to our data. Variant chr8-143916158-G-A is described in ClinVar as [Benign]. Clinvar id is 93013.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.153 is higher than 0.05.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes 0.0451 AC: 6865AN: 152162Hom.: 539 Cov.: 34 show subpopulations
GnomAD3 genomes
AF:
AC:
6865
AN:
152162
Hom.:
Cov.:
34
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
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Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD2 exomes AF: 0.00935 AC: 1209AN: 129348 AF XY: 0.00767 show subpopulations
GnomAD2 exomes
AF:
AC:
1209
AN:
129348
AF XY:
Gnomad AFR exome
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Gnomad AMR exome
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Gnomad ASJ exome
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Gnomad EAS exome
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Gnomad FIN exome
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Gnomad NFE exome
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Gnomad OTH exome
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GnomAD4 exome AF: 0.00452 AC: 6196AN: 1369702Hom.: 479 Cov.: 28 AF XY: 0.00396 AC XY: 2669AN XY: 674106 show subpopulations
GnomAD4 exome
AF:
AC:
6196
AN:
1369702
Hom.:
Cov.:
28
AF XY:
AC XY:
2669
AN XY:
674106
show subpopulations
African (AFR)
AF:
AC:
4983
AN:
30268
American (AMR)
AF:
AC:
293
AN:
32552
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
24122
East Asian (EAS)
AF:
AC:
1
AN:
35276
South Asian (SAS)
AF:
AC:
39
AN:
77196
European-Finnish (FIN)
AF:
AC:
0
AN:
42414
Middle Eastern (MID)
AF:
AC:
18
AN:
3996
European-Non Finnish (NFE)
AF:
AC:
256
AN:
1067146
Other (OTH)
AF:
AC:
606
AN:
56732
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.487
Heterozygous variant carriers
0
260
520
781
1041
1301
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.0452 AC: 6885AN: 152280Hom.: 543 Cov.: 34 AF XY: 0.0431 AC XY: 3211AN XY: 74478 show subpopulations
GnomAD4 genome
AF:
AC:
6885
AN:
152280
Hom.:
Cov.:
34
AF XY:
AC XY:
3211
AN XY:
74478
show subpopulations
African (AFR)
AF:
AC:
6488
AN:
41534
American (AMR)
AF:
AC:
285
AN:
15308
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3468
East Asian (EAS)
AF:
AC:
0
AN:
5184
South Asian (SAS)
AF:
AC:
4
AN:
4828
European-Finnish (FIN)
AF:
AC:
0
AN:
10630
Middle Eastern (MID)
AF:
AC:
6
AN:
292
European-Non Finnish (NFE)
AF:
AC:
32
AN:
68014
Other (OTH)
AF:
AC:
70
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.501
Heterozygous variant carriers
0
305
610
916
1221
1526
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
25
AN:
3478
ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:not provided
- -
Mar 03, 2015
GeneDx
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
not specified Benign:1
May 20, 2016
Eurofins Ntd Llc (ga)
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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