rs782656592
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_001105206.3(LAMA4):c.157C>T(p.Pro53Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000976 in 1,433,972 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000098 ( 0 hom. )
Consequence
LAMA4
NM_001105206.3 missense
NM_001105206.3 missense
Scores
19
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.459
Genes affected
LAMA4 (HGNC:6484): (laminin subunit alpha 4) Laminins, a family of extracellular matrix glycoproteins, are the major noncollagenous constituent of basement membranes. They have been implicated in a wide variety of biological processes including cell adhesion, differentiation, migration, signaling, neurite outgrowth and metastasis. Laminins are composed of 3 non identical chains: laminin alpha, beta and gamma (formerly A, B1, and B2, respectively) and they form a cruciform structure consisting of 3 short arms, each formed by a different chain, and a long arm composed of all 3 chains. Each laminin chain is a multidomain protein encoded by a distinct gene. Several isoforms of each chain have been described. Different alpha, beta and gamma chain isomers combine to give rise to different heterotrimeric laminin isoforms which are designated by Arabic numerals in the order of their discovery, i.e. alpha1beta1gamma1 heterotrimer is laminin 1. The biological functions of the different chains and trimer molecules are largely unknown, but some of the chains have been shown to differ with respect to their tissue distribution, presumably reflecting diverse functions in vivo. This gene encodes the alpha chain isoform laminin, alpha 4. The domain structure of alpha 4 is similar to that of alpha 3, both of which resemble truncated versions of alpha 1 and alpha 2, in that approximately 1,200 residues at the N-terminus (domains IV, V and VI) have been lost. Laminin, alpha 4 contains the C-terminal G domain which distinguishes all alpha chains from the beta and gamma chains. The RNA analysis from adult and fetal tissues revealed developmental regulation of expression, however, the exact function of laminin, alpha 4 is not known. Tissue-specific utilization of alternative polyA-signal has been described in literature. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Aug 2011]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.04678887).
BS2
High AC in GnomAdExome4 at 14 AD gene.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| LAMA4 | NM_001105206.3 | c.157C>T | p.Pro53Ser | missense_variant | Exon 2 of 39 | ENST00000230538.12 | NP_001098676.2 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| LAMA4 | ENST00000230538.12 | c.157C>T | p.Pro53Ser | missense_variant | Exon 2 of 39 | 1 | NM_001105206.3 | ENSP00000230538.7 | ||
| ENSG00000281613 | ENST00000587816.2 | c.-398+17078G>A | intron_variant | Intron 1 of 4 | 5 | ENSP00000487146.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD3 exomes AF: 0.00000503 AC: 1AN: 198682Hom.: 0 AF XY: 0.00000934 AC XY: 1AN XY: 107032
GnomAD3 exomes
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GnomAD4 exome AF: 0.00000976 AC: 14AN: 1433972Hom.: 0 Cov.: 31 AF XY: 0.0000141 AC XY: 10AN XY: 710934
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GnomAD4 genome
GnomAD4 genome
Cov.:
32
ExAC
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1
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;T;T;T;.;T;.;.;T;.;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;.;.;T;T;T;T;T;T;.;.;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
.;.;.;.;.;.;.;.;.;N;N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N;N;N;N;N;D;D;D;D;D
REVEL
Benign
Sift
Benign
T;T;T;T;T;T;T;T;T;T;T;T
Sift4G
Benign
T;T;T;T;.;.;T;.;.;D;D;.
Polyphen
0.0070, 0.019
.;.;.;.;.;.;B;.;.;B;B;B
Vest4
MutPred
Gain of phosphorylation at P53 (P = 0.0213);Gain of phosphorylation at P53 (P = 0.0213);Gain of phosphorylation at P53 (P = 0.0213);Gain of phosphorylation at P53 (P = 0.0213);Gain of phosphorylation at P53 (P = 0.0213);Gain of phosphorylation at P53 (P = 0.0213);Gain of phosphorylation at P53 (P = 0.0213);Gain of phosphorylation at P53 (P = 0.0213);Gain of phosphorylation at P53 (P = 0.0213);Gain of phosphorylation at P53 (P = 0.0213);Gain of phosphorylation at P53 (P = 0.0213);Gain of phosphorylation at P53 (P = 0.0213);
MVP
MPC
ClinPred
T
GERP RS
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