rs7660664
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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.7110C>T(p.His2370=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 1,613,504 control chromosomes in the GnomAD database, including 100,913 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.37 ( 11113 hom., cov: 32)
Exomes 𝑓: 0.35 ( 89800 hom. )
Consequence
FRAS1
NM_025074.7 synonymous
NM_025074.7 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0430
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=-0.66).
BP6
?
Variant 4-78466288-C-T is Benign according to our data. Variant chr4-78466288-C-T is described in ClinVar as [Benign]. Clinvar id is 261812.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-78466288-C-T is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=-0.043 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.48 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FRAS1 | NM_025074.7 | c.7110C>T | p.His2370= | synonymous_variant | 50/74 | ENST00000512123.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FRAS1 | ENST00000512123.4 | c.7110C>T | p.His2370= | synonymous_variant | 50/74 | 5 | NM_025074.7 | P1 | |
FRAS1 | ENST00000682513.1 | c.7110C>T | p.His2370= | synonymous_variant | 50/64 |
Frequencies
GnomAD3 genomes ? AF: 0.373 AC: 56744AN: 151962Hom.: 11097 Cov.: 32
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GnomAD3 exomes AF: 0.311 AC: 77544AN: 249080Hom.: 13041 AF XY: 0.306 AC XY: 41347AN XY: 135076
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GnomAD4 exome AF: 0.346 AC: 505158AN: 1461424Hom.: 89800 Cov.: 44 AF XY: 0.340 AC XY: 247057AN XY: 727012
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GnomAD4 genome ? AF: 0.373 AC: 56798AN: 152080Hom.: 11113 Cov.: 32 AF XY: 0.366 AC XY: 27217AN XY: 74346
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ClinVar
Significance: Benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Nov 09, 2016 | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Fraser syndrome 1 Benign:2
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. - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Aug 10, 2021 | - - |
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