rs2076355
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000228.3(LAMB3):c.298+50T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.295 in 1,231,534 control chromosomes in the GnomAD database, including 61,159 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.30 ( 7612 hom., cov: 33)
Exomes 𝑓: 0.29 ( 53547 hom. )
Consequence
LAMB3
NM_000228.3 intron
NM_000228.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.829
Genes affected
LAMB3 (HGNC:6490): (laminin subunit beta 3) The product encoded by this gene is a laminin that belongs to a family of basement membrane proteins. This protein is a beta subunit laminin, which together with an alpha and a gamma subunit, forms laminin-5. Mutations in this gene cause epidermolysis bullosa junctional Herlitz type, and generalized atrophic benign epidermolysis bullosa, diseases that are characterized by blistering of the skin. Multiple alternatively spliced transcript variants that encode the same protein have been found for this gene. [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=-0.82).
BP6
Variant 1-209638484-A-T is Benign according to our data. Variant chr1-209638484-A-T is described in ClinVar as [Benign]. Clinvar id is 255593.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.703 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LAMB3 | NM_000228.3 | c.298+50T>A | intron_variant | ENST00000356082.9 | NP_000219.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LAMB3 | ENST00000356082.9 | c.298+50T>A | intron_variant | 1 | NM_000228.3 | ENSP00000348384.3 | ||||
LAMB3 | ENST00000367030.7 | c.298+50T>A | intron_variant | 1 | ENSP00000355997.3 | |||||
LAMB3 | ENST00000391911.5 | c.298+50T>A | intron_variant | 1 | ENSP00000375778.1 | |||||
LAMB3 | ENST00000415782.1 | c.298+50T>A | intron_variant | 2 | ENSP00000388960.1 |
Frequencies
GnomAD3 genomes AF: 0.301 AC: 45228AN: 150420Hom.: 7599 Cov.: 33
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GnomAD3 exomes AF: 0.346 AC: 86095AN: 249054Hom.: 17777 AF XY: 0.344 AC XY: 46262AN XY: 134676
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GnomAD4 exome AF: 0.294 AC: 317628AN: 1080994Hom.: 53547 Cov.: 15 AF XY: 0.298 AC XY: 165111AN XY: 554946
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GnomAD4 genome AF: 0.301 AC: 45278AN: 150540Hom.: 7612 Cov.: 33 AF XY: 0.310 AC XY: 22807AN XY: 73602
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ClinVar
Significance: Benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Junctional epidermolysis bullosa, non-Herlitz type Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 08, 2021 | - - |
Amelogenesis imperfecta type 1A Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 08, 2021 | - - |
Junctional epidermolysis bullosa gravis of Herlitz Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 08, 2021 | - - |
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