rs12208872
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The ENST00000230538.12(LAMA4):c.*460T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 178,152 control chromosomes in the GnomAD database, including 5,574 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.25 ( 4733 hom., cov: 32)
Exomes 𝑓: 0.23 ( 841 hom. )
Consequence
LAMA4
ENST00000230538.12 3_prime_UTR
ENST00000230538.12 3_prime_UTR
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.573
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 -12 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.311 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LAMA4 | NM_001105206.3 | c.*460T>C | 3_prime_UTR_variant | 39/39 | ENST00000230538.12 | NP_001098676.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LAMA4 | ENST00000230538.12 | c.*460T>C | 3_prime_UTR_variant | 39/39 | 1 | NM_001105206.3 | ENSP00000230538 | A1 | ||
LAMA4 | ENST00000389463.9 | c.*460T>C | 3_prime_UTR_variant | 39/39 | 1 | ENSP00000374114 | P4 | |||
LAMA4 | ENST00000522006.5 | c.*460T>C | 3_prime_UTR_variant | 39/39 | 1 | ENSP00000429488 | P4 |
Frequencies
GnomAD3 genomes AF: 0.249 AC: 37873AN: 152052Hom.: 4734 Cov.: 32
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GnomAD4 exome AF: 0.234 AC: 6074AN: 25980Hom.: 841 Cov.: 0 AF XY: 0.223 AC XY: 2933AN XY: 13128
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GnomAD4 genome AF: 0.249 AC: 37894AN: 152172Hom.: 4733 Cov.: 32 AF XY: 0.244 AC XY: 18161AN XY: 74400
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ClinVar
Not reported inComputational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at