2-181536766-A-ACAAT
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_000885.6(ITGA4):c.*1242_*1245dupATCA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00151 in 248,654 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0022 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00034 ( 0 hom. )
Consequence
ITGA4
NM_000885.6 3_prime_UTR
NM_000885.6 3_prime_UTR
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -4.85
Genes affected
ITGA4 (HGNC:6140): (integrin subunit alpha 4) The gene encodes a member of the integrin alpha chain family of proteins. Integrins are heterodimeric integral membrane proteins composed of an alpha chain and a beta chain that function in cell surface adhesion and signaling. The encoded preproprotein is proteolytically processed to generate light and heavy chains that comprise the alpha 4 subunit. This subunit associates with a beta 1 or beta 7 subunit to form an integrin that may play a role in cell motility and migration. This integrin is a therapeutic target for the treatment of multiple sclerosis, Crohn's disease and inflammatory bowel disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2015]
CERKL (HGNC:21699): (ceramide kinase like) This gene was initially identified as a locus (RP26) associated with an autosomal recessive form of retinitis pigmentosa (arRP) disease. This gene encodes a protein with ceramide kinase-like domains, however, the protein does not phosphorylate ceramide and its target substrate is currently unknown. This protein may be a negative regulator of apoptosis in photoreceptor cells. Mutations in this gene cause a form of retinitis pigmentosa characterized by autosomal recessive cone and rod dystrophy (arCRD). Alternative splicing of this gene results in multiple transcript variants encoding different isoforms and non-coding transcripts.[provided by RefSeq, May 2010]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
BS2
High AC in GnomAd4 at 342 AD gene.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ITGA4 | ENST00000397033.7 | c.*1242_*1245dupATCA | 3_prime_UTR_variant | 28/28 | 1 | NM_000885.6 | ENSP00000380227.2 | |||
CERKL | ENST00000410087 | c.*1414_*1417dupATTG | 3_prime_UTR_variant | 13/13 | 1 | NM_201548.5 | ENSP00000386725.3 | |||
CERKL | ENST00000684145 | c.*1414_*1417dupATTG | 3_prime_UTR_variant | 12/12 | ENSP00000508396.1 |
Frequencies
GnomAD3 genomes AF: 0.00223 AC: 339AN: 152078Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000890 AC: 23AN: 25830Hom.: 0 AF XY: 0.000585 AC XY: 8AN XY: 13682
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GnomAD4 exome AF: 0.000342 AC: 33AN: 96458Hom.: 0 Cov.: 0 AF XY: 0.000268 AC XY: 14AN XY: 52220
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GnomAD4 genome AF: 0.00225 AC: 342AN: 152196Hom.: 0 Cov.: 33 AF XY: 0.00231 AC XY: 172AN XY: 74424
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Retinitis Pigmentosa, Recessive Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at