rs13123710
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Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1
The NM_025074.7(FRAS1):c.6924C>T(p.Val2308=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0736 in 1,613,782 control chromosomes in the GnomAD database, including 5,030 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.055 ( 325 hom., cov: 32)
Exomes 𝑓: 0.075 ( 4705 hom. )
Consequence
FRAS1
NM_025074.7 synonymous
NM_025074.7 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.79
Genes affected
FRAS1 (HGNC:19185): (Fraser extracellular matrix complex subunit 1) This gene encodes an extracellular matrix protein that appears to function in the regulation of epidermal-basement membrane adhesion and organogenesis during development. Mutations in this gene cause Fraser syndrome, a multisystem malformation that can include craniofacial, urogenital and respiratory system abnormalities. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -19 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.32).
BP6
?
Variant 4-78464478-C-T is Benign according to our data. Variant chr4-78464478-C-T is described in ClinVar as [Benign]. Clinvar id is 261810.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-78464478-C-T is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=2.79 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0819 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FRAS1 | NM_025074.7 | c.6924C>T | p.Val2308= | synonymous_variant | 49/74 | ENST00000512123.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FRAS1 | ENST00000512123.4 | c.6924C>T | p.Val2308= | synonymous_variant | 49/74 | 5 | NM_025074.7 | P1 | |
FRAS1 | ENST00000682513.1 | c.6924C>T | p.Val2308= | synonymous_variant | 49/64 |
Frequencies
GnomAD3 genomes ? AF: 0.0552 AC: 8393AN: 152126Hom.: 326 Cov.: 32
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GnomAD3 exomes AF: 0.0575 AC: 14312AN: 248878Hom.: 571 AF XY: 0.0582 AC XY: 7851AN XY: 135002
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GnomAD4 exome AF: 0.0755 AC: 110315AN: 1461538Hom.: 4705 Cov.: 32 AF XY: 0.0742 AC XY: 53939AN XY: 727068
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GnomAD4 genome ? AF: 0.0551 AC: 8391AN: 152244Hom.: 325 Cov.: 32 AF XY: 0.0539 AC XY: 4009AN XY: 74432
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Fraser syndrome 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 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. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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