chr11-65654381-G-A
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_021975.4(RELA):c.1653C>T(p.Ser551=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000768 in 1,613,596 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0036 ( 1 hom., cov: 33)
Exomes 𝑓: 0.00047 ( 5 hom. )
Consequence
RELA
NM_021975.4 synonymous
NM_021975.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.528
Genes affected
RELA (HGNC:9955): (RELA proto-oncogene, NF-kB subunit) NF-kappa-B is a ubiquitous transcription factor involved in several biological processes. It is held in the cytoplasm in an inactive state by specific inhibitors. Upon degradation of the inhibitor, NF-kappa-B moves to the nucleus and activates transcription of specific genes. NF-kappa-B is composed of NFKB1 or NFKB2 bound to either REL, RELA, or RELB. The most abundant form of NF-kappa-B is NFKB1 complexed with the product of this gene, RELA. Four transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]
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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=-0.62).
BP6
?
Variant 11-65654381-G-A is Benign according to our data. Variant chr11-65654381-G-A is described in ClinVar as [Benign]. Clinvar id is 730838.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.528 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00363 (553/152350) while in subpopulation AFR AF= 0.0123 (510/41586). AF 95% confidence interval is 0.0114. There are 1 homozygotes in gnomad4. There are 271 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High AC in GnomAd at 549 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RELA | NM_021975.4 | c.1653C>T | p.Ser551= | synonymous_variant | 11/11 | ENST00000406246.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RELA | ENST00000406246.8 | c.1653C>T | p.Ser551= | synonymous_variant | 11/11 | 1 | NM_021975.4 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.00361 AC: 549AN: 152232Hom.: 1 Cov.: 33
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GnomAD3 exomes AF: 0.00102 AC: 254AN: 249504Hom.: 1 AF XY: 0.000783 AC XY: 106AN XY: 135294
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GnomAD4 exome AF: 0.000470 AC: 687AN: 1461246Hom.: 5 Cov.: 31 AF XY: 0.000411 AC XY: 299AN XY: 726930
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
RELA-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 06, 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 | Jan 25, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
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Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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