chr17-40356136-C-T
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2
The NM_000964.4(RARA):c.1299C>T(p.Asp433=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000458 in 1,486,016 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.00019 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000032 ( 0 hom. )
Consequence
RARA
NM_000964.4 synonymous
NM_000964.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.27
Genes affected
RARA (HGNC:9864): (retinoic acid receptor alpha) This gene represents a nuclear retinoic acid receptor. The encoded protein, retinoic acid receptor alpha, regulates transcription in a ligand-dependent manner. This gene has been implicated in regulation of development, differentiation, apoptosis, granulopoeisis, and transcription of clock genes. Translocations between this locus and several other loci have been associated with acute promyelocytic leukemia. Alternatively spliced transcript variants have been found for this locus.[provided by RefSeq, Sep 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.57).
BP6
?
Variant 17-40356136-C-T is Benign according to our data. Variant chr17-40356136-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 745170.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-1.27 with no splicing effect.
BS2
?
High AC in GnomAd at 24 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RARA | NM_000964.4 | c.1299C>T | p.Asp433= | synonymous_variant | 9/9 | ENST00000254066.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RARA | ENST00000254066.10 | c.1299C>T | p.Asp433= | synonymous_variant | 9/9 | 1 | NM_000964.4 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.000194 AC: 24AN: 123522Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.000143 AC: 21AN: 147068Hom.: 0 AF XY: 0.000151 AC XY: 12AN XY: 79700
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GnomAD4 exome AF: 0.0000323 AC: 44AN: 1362494Hom.: 0 Cov.: 38 AF XY: 0.0000387 AC XY: 26AN XY: 671840
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GnomAD4 genome ? AF: 0.000194 AC: 24AN: 123522Hom.: 0 Cov.: 31 AF XY: 0.000297 AC XY: 18AN XY: 60552
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | May 21, 2018 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at