rs2710555
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Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1
The NM_001291303.3(FAT4):c.4305C>T(p.Ile1435Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.704 in 1,613,428 control chromosomes in the GnomAD database, including 403,225 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.73 ( 41728 hom., cov: 33)
Exomes 𝑓: 0.70 ( 361497 hom. )
Consequence
FAT4
NM_001291303.3 synonymous
NM_001291303.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.852
Genes affected
FAT4 (HGNC:23109): (FAT atypical cadherin 4) The protein encoded by this gene is a member of the protocadherin family. This gene may play a role in regulating planar cell polarity (PCP). Studies in mice suggest that loss of PCP signaling may cause cystic kidney disease, and mutations in this gene have been associated with Van Maldergem Syndrome 2. Alternatively spliced transcript variants have been noted for this gene. [provided by RefSeq, Mar 2014]
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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 4-125320716-C-T is Benign according to our data. Variant chr4-125320716-C-T is described in ClinVar as [Benign]. Clinvar id is 377855.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-125320716-C-T is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=0.852 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.849 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FAT4 | NM_001291303.3 | c.4305C>T | p.Ile1435Ile | synonymous_variant | 2/18 | ENST00000394329.9 | NP_001278232.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FAT4 | ENST00000394329.9 | c.4305C>T | p.Ile1435Ile | synonymous_variant | 2/18 | 5 | NM_001291303.3 | ENSP00000377862.4 | ||
FAT4 | ENST00000674496.2 | c.-55+4739C>T | intron_variant | ENSP00000501473.2 | ||||||
FAT4 | ENST00000678072.1 | n.1911C>T | non_coding_transcript_exon_variant | 1/2 |
Frequencies
GnomAD3 genomes AF: 0.734 AC: 111548AN: 152058Hom.: 41663 Cov.: 33
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GnomAD3 exomes AF: 0.691 AC: 172243AN: 249316Hom.: 60491 AF XY: 0.692 AC XY: 93656AN XY: 135268
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GnomAD4 exome AF: 0.701 AC: 1024607AN: 1461252Hom.: 361497 Cov.: 48 AF XY: 0.702 AC XY: 510616AN XY: 726978
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GnomAD4 genome AF: 0.734 AC: 111672AN: 152176Hom.: 41728 Cov.: 33 AF XY: 0.726 AC XY: 53989AN XY: 74360
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ClinVar
Significance: Benign
Submissions summary: Benign:9
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:5
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 29, 2016 | Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: 70% of total chromosomes in ExAC - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 08, 2016 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan | Jan 24, 2024 | This variant is classified as Benign based on local population frequency. This variant was detected in 95% of patients studied by a panel of primary immunodeficiencies. Number of patients: 90. Only high quality variants are reported. - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
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 | - - |
Van Maldergem syndrome 2 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Aug 10, 2021 | - - |
Hennekam lymphangiectasia-lymphedema syndrome 2 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Aug 10, 2021 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
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