9-14737454-TG-T
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PVS1_Moderate
The NM_001379081.2(FREM1):c.6481delC(p.Gln2161LysfsTer51) variant causes a frameshift change. The variant allele was found at a frequency of 0.00000496 in 1,613,770 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000027 ( 0 hom. )
Consequence
FREM1
NM_001379081.2 frameshift
NM_001379081.2 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 6.92
Genes affected
FREM1 (HGNC:23399): (FRAS1 related extracellular matrix 1) This gene encodes a basement membrane protein that may play a role in craniofacial and renal development. Mutations in this gene have been associated with bifid nose with or without anorectal and renal anomalies. Alternatively spliced transcript variants encoding different isoforms have been described. PubMed ID 19940113 describes one such variant that initiates transcription within a distinct, internal exon; the resulting shorter isoform (named Toll-like/interleukin-1 receptor regulator, TILRR) is suggested to be a co-receptor of the interleukin 1 receptor family and may regulate receptor function and Toll-like receptor/interleukin 1 receptor signal transduction, contributing to the control of inflammatory response activation. [provided by RefSeq, Apr 2011]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.00902 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FREM1 | NM_001379081.2 | c.6481delC | p.Gln2161LysfsTer51 | frameshift_variant | Exon 37 of 37 | ENST00000380880.4 | NP_001366010.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152132Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000803 AC: 2AN: 249060Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135136
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GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461638Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2AN XY: 727098
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GnomAD4 genome AF: 0.0000263 AC: 4AN: 152132Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74320
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Oculotrichoanal syndrome;C2750433:BNAR syndrome;C3280974:Trigonocephaly 2 Uncertain:1
Feb 09, 2024
Fulgent Genetics, Fulgent Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at