rs10733289
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_001379081.2(FREM1):c.4785C>T(p.Ala1595=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.549 in 1,612,504 control chromosomes in the GnomAD database, including 249,104 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.48 ( 18981 hom., cov: 32)
Exomes 𝑓: 0.56 ( 230123 hom. )
Consequence
FREM1
NM_001379081.2 synonymous
NM_001379081.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.642
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 Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.59).
BP6
?
Variant 9-14775861-G-A is Benign according to our data. Variant chr9-14775861-G-A is described in ClinVar as [Benign]. Clinvar id is 262541.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-14775861-G-A is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=0.642 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.579 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FREM1 | NM_001379081.2 | c.4785C>T | p.Ala1595= | synonymous_variant | 25/37 | ENST00000380880.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FREM1 | ENST00000380880.4 | c.4785C>T | p.Ala1595= | synonymous_variant | 25/37 | 5 | NM_001379081.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.485 AC: 73660AN: 151880Hom.: 18967 Cov.: 32
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GnomAD3 exomes AF: 0.506 AC: 126023AN: 249074Hom.: 33417 AF XY: 0.511 AC XY: 69107AN XY: 135124
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GnomAD4 exome AF: 0.556 AC: 811472AN: 1460506Hom.: 230123 Cov.: 46 AF XY: 0.553 AC XY: 402145AN XY: 726564
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GnomAD4 genome ? AF: 0.485 AC: 73694AN: 151998Hom.: 18981 Cov.: 32 AF XY: 0.484 AC XY: 35957AN XY: 74308
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ClinVar
Significance: Benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Oculotrichoanal syndrome Benign:2
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Aug 10, 2021 | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 28, 2020 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
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DANN
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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