chr1-209628065-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP6_Moderate
The NM_000228.3(LAMB3):c.1258C>G(p.Leu420Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000796 in 1,607,418 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position (i.e. L420L) has been classified as Likely benign.
Frequency
Genomes: 𝑓 0.000059 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000082 ( 0 hom. )
Consequence
LAMB3
NM_000228.3 missense
NM_000228.3 missense
Scores
12
6
Clinical Significance
Conservation
PhyloP100: 6.11
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 Uncertain_significance. Variant got 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP6
?
Variant 1-209628065-G-C is Benign according to our data. Variant chr1-209628065-G-C is described in ClinVar as [Benign]. Clinvar id is 255583.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LAMB3 | NM_000228.3 | c.1258C>G | p.Leu420Val | missense_variant | 11/23 | ENST00000356082.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LAMB3 | ENST00000356082.9 | c.1258C>G | p.Leu420Val | missense_variant | 11/23 | 1 | NM_000228.3 | P1 | |
LAMB3 | ENST00000367030.7 | c.1258C>G | p.Leu420Val | missense_variant | 11/23 | 1 | P1 | ||
LAMB3 | ENST00000391911.5 | c.1258C>G | p.Leu420Val | missense_variant | 10/22 | 1 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000591 AC: 9AN: 152208Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000801 AC: 19AN: 237212Hom.: 0 AF XY: 0.000101 AC XY: 13AN XY: 128430
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GnomAD4 exome AF: 0.0000818 AC: 119AN: 1455092Hom.: 0 Cov.: 33 AF XY: 0.0000802 AC XY: 58AN XY: 723106
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GnomAD4 genome ? AF: 0.0000591 AC: 9AN: 152326Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74480
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Benign
T;T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;M
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
N;N;N
REVEL
Uncertain
Sift
Uncertain
D;D;D
Sift4G
Uncertain
D;D;D
Polyphen
D;D;D
Vest4
MVP
MPC
0.51
ClinPred
T
GERP RS
Varity_R
gMVP
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