rs6851427
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_025074.7(FRAS1):c.7011G>A(p.Ala2337=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 1,613,104 control chromosomes in the GnomAD database, including 109,444 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.33 ( 8800 hom., cov: 31)
Exomes 𝑓: 0.37 ( 100644 hom. )
Consequence
FRAS1
NM_025074.7 synonymous
NM_025074.7 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.52
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 -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
Variant 4-78464565-G-A is Benign according to our data. Variant chr4-78464565-G-A is described in ClinVar as [Benign]. Clinvar id is 261811.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-78464565-G-A is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=-2.53 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.399 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FRAS1 | NM_025074.7 | c.7011G>A | p.Ala2337= | synonymous_variant | 49/74 | ENST00000512123.4 | NP_079350.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FRAS1 | ENST00000512123.4 | c.7011G>A | p.Ala2337= | synonymous_variant | 49/74 | 5 | NM_025074.7 | ENSP00000422834 | P1 | |
FRAS1 | ENST00000682513.1 | c.7011G>A | p.Ala2337= | synonymous_variant | 49/64 | ENSP00000508201 |
Frequencies
GnomAD3 genomes AF: 0.326 AC: 49493AN: 151860Hom.: 8787 Cov.: 31
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GnomAD3 exomes AF: 0.371 AC: 92053AN: 248356Hom.: 17953 AF XY: 0.366 AC XY: 49251AN XY: 134672
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GnomAD4 exome AF: 0.367 AC: 536916AN: 1461126Hom.: 100644 Cov.: 41 AF XY: 0.366 AC XY: 266054AN XY: 726828
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GnomAD4 genome AF: 0.326 AC: 49534AN: 151978Hom.: 8800 Cov.: 31 AF XY: 0.329 AC XY: 24410AN XY: 74258
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ClinVar
Significance: Benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Fraser syndrome 1 Benign:3
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
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 specified Benign:2
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
not provided Benign:2
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 01, 2024 | - - |
Computational scores
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BayesDel_noAF
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CADD
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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