rs78040862
Positions:
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_001291303.3(FAT4):āc.12855T>Cā(p.Asp4285=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00487 in 1,613,850 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.0036 ( 0 hom., cov: 32)
Exomes š: 0.0050 ( 31 hom. )
Consequence
FAT4
NM_001291303.3 synonymous
NM_001291303.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.22
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 -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.52).
BP6
?
Variant 4-125487377-T-C is Benign according to our data. Variant chr4-125487377-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 380888.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-125487377-T-C is described in Lovd as [Likely_benign]. Variant chr4-125487377-T-C is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=1.22 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00363 (553/152338) while in subpopulation NFE AF= 0.00554 (377/68034). AF 95% confidence interval is 0.00508. There are 0 homozygotes in gnomad4. There are 250 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAdExome4 at 31 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FAT4 | NM_001291303.3 | c.12855T>C | p.Asp4285= | synonymous_variant | 17/18 | ENST00000394329.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FAT4 | ENST00000394329.9 | c.12855T>C | p.Asp4285= | synonymous_variant | 17/18 | 5 | NM_001291303.3 | P1 | |
FAT4 | ENST00000335110.5 | c.7572T>C | p.Asp2524= | synonymous_variant | 14/15 | 1 | |||
FAT4 | ENST00000674496.2 | c.7626T>C | p.Asp2542= | synonymous_variant | 16/17 |
Frequencies
GnomAD3 genomes ? AF: 0.00363 AC: 552AN: 152220Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00495 AC: 1241AN: 250696Hom.: 9 AF XY: 0.00537 AC XY: 728AN XY: 135626
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GnomAD4 exome AF: 0.00500 AC: 7308AN: 1461512Hom.: 31 Cov.: 31 AF XY: 0.00513 AC XY: 3727AN XY: 727020
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GnomAD4 genome ? AF: 0.00363 AC: 553AN: 152338Hom.: 0 Cov.: 32 AF XY: 0.00336 AC XY: 250AN XY: 74498
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2024 | FAT4: BP4, BP7, BS2 - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Sep 07, 2023 | - - |
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 05, 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. - |
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jun 05, 2018 | - - |
FAT4-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | May 15, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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Name
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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