chr6-7181998-G-A
Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_001003699.4(RREB1):c.87G>A(p.Lys29=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000662 in 1,613,814 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0027 ( 2 hom., cov: 32)
Exomes 𝑓: 0.00045 ( 5 hom. )
Consequence
RREB1
NM_001003699.4 synonymous
NM_001003699.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.09
Genes affected
RREB1 (HGNC:10449): (ras responsive element binding protein 1) The protein encoded by this gene is a zinc finger transcription factor that binds to RAS-responsive elements (RREs) of gene promoters. It has been shown that the calcitonin gene promoter contains an RRE and that the encoded protein binds there and increases expression of calcitonin, which may be involved in Ras/Raf-mediated cell differentiation. Multiple transcript variants encoding several different isoforms have been found for this gene. [provided by RefSeq, Dec 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.51).
BP6
?
Variant 6-7181998-G-A is Benign according to our data. Variant chr6-7181998-G-A is described in ClinVar as [Benign]. Clinvar id is 791535.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=2.09 with no splicing effect.
BS2
?
High AC in GnomAd at 407 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RREB1 | NM_001003699.4 | c.87G>A | p.Lys29= | synonymous_variant | 4/13 | ENST00000379938.7 | |
RREB1 | NM_001003698.4 | c.87G>A | p.Lys29= | synonymous_variant | 4/12 | ||
RREB1 | NM_001168344.2 | c.87G>A | p.Lys29= | synonymous_variant | 4/12 | ||
RREB1 | NM_001003700.2 | c.87G>A | p.Lys29= | synonymous_variant | 4/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RREB1 | ENST00000379938.7 | c.87G>A | p.Lys29= | synonymous_variant | 4/13 | 1 | NM_001003699.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00268 AC: 407AN: 151826Hom.: 2 Cov.: 32
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GnomAD3 exomes AF: 0.000804 AC: 202AN: 251392Hom.: 0 AF XY: 0.000662 AC XY: 90AN XY: 135860
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GnomAD4 exome AF: 0.000451 AC: 659AN: 1461870Hom.: 5 Cov.: 31 AF XY: 0.000433 AC XY: 315AN XY: 727242
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
RREB1-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 25, 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). - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2019 | - - |
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