rs117691319
Positions:
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_021008.4(DEAF1):c.774C>T(p.Tyr258=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0117 in 1,614,214 control chromosomes in the GnomAD database, including 123 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.010 ( 12 hom., cov: 33)
Exomes 𝑓: 0.012 ( 111 hom. )
Consequence
DEAF1
NM_021008.4 synonymous
NM_021008.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.352
Genes affected
DEAF1 (HGNC:14677): (DEAF1 transcription factor) This gene encodes a zinc finger domain-containing protein that functions as a regulator of transcription. The encoded proteins binds to its own promoter as well as to that of several target genes. Activity of this protein is important in the regulation of embryonic development. Mutations in this gene have been found in individuals with autosomal dominant cognitive disability. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 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=-0.48).
BP6
?
Variant 11-686888-G-A is Benign according to our data. Variant chr11-686888-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 447242.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.352 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00997 (1519/152346) while in subpopulation NFE AF= 0.0141 (959/68032). AF 95% confidence interval is 0.0134. There are 12 homozygotes in gnomad4. There are 782 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 12 SD gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DEAF1 | NM_021008.4 | c.774C>T | p.Tyr258= | synonymous_variant | 5/12 | ENST00000382409.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DEAF1 | ENST00000382409.4 | c.774C>T | p.Tyr258= | synonymous_variant | 5/12 | 1 | NM_021008.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00998 AC: 1519AN: 152230Hom.: 12 Cov.: 33
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GnomAD3 exomes AF: 0.0103 AC: 2594AN: 251178Hom.: 29 AF XY: 0.0104 AC XY: 1418AN XY: 135812
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GnomAD4 exome AF: 0.0119 AC: 17416AN: 1461868Hom.: 111 Cov.: 33 AF XY: 0.0117 AC XY: 8521AN XY: 727232
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GnomAD4 genome ? AF: 0.00997 AC: 1519AN: 152346Hom.: 12 Cov.: 33 AF XY: 0.0105 AC XY: 782AN XY: 74502
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2024 | DEAF1: BP4, BP7, BS1, BS2 - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jul 07, 2017 | - - |
Intellectual disability, autosomal dominant 24;C4310683:Intellectual disability-epilepsy-extrapyramidal syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Jan 21, 2022 | - - |
DEAF1-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 08, 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
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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