X-53422829-C-T
Variant names:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The ENST00000329209(RIBC1):c.-181C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0465 in 362,286 control chromosomes in the GnomAD database, including 405 homozygotes. There are 4,801 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.041 ( 126 hom., 1375 hem., cov: 24)
Exomes 𝑓: 0.049 ( 279 hom. 3426 hem. )
Consequence
RIBC1
ENST00000329209 5_prime_UTR
ENST00000329209 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.333
Genes affected
RIBC1 (HGNC:26537): (RIB43A domain with coiled-coils 1)
SMC1A (HGNC:11111): (structural maintenance of chromosomes 1A) Proper cohesion of sister chromatids is a prerequisite for the correct segregation of chromosomes during cell division. The cohesin multiprotein complex is required for sister chromatid cohesion. This complex is composed partly of two structural maintenance of chromosomes (SMC) proteins, SMC3 and either SMC1B or the protein encoded by this gene. Most of the cohesin complexes dissociate from the chromosomes before mitosis, although those complexes at the kinetochore remain. Therefore, the encoded protein is thought to be an important part of functional kinetochores. In addition, this protein interacts with BRCA1 and is phosphorylated by ATM, indicating a potential role for this protein in DNA repair. This gene, which belongs to the SMC gene family, is located in an area of the X-chromosome that escapes X inactivation. Mutations in this gene result in Cornelia de Lange syndrome. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2013]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.76).
BP6
Variant X-53422829-C-T is Benign according to our data. Variant chrX-53422829-C-T is described in ClinVar as [Benign]. Clinvar id is 1226124.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0634 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SMC1A | NM_006306.4 | c.-229G>A | upstream_gene_variant | ENST00000322213.9 | NP_006297.2 | |||
RIBC1 | NM_001031745.5 | c.-265C>T | upstream_gene_variant | ENST00000375327.6 | NP_001026915.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0414 AC: 4680AN: 112917Hom.: 126 Cov.: 24 AF XY: 0.0393 AC XY: 1376AN XY: 35055
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GnomAD4 exome AF: 0.0488 AC: 12179AN: 249318Hom.: 279 Cov.: 0 AF XY: 0.0457 AC XY: 3426AN XY: 74946
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GnomAD4 genome AF: 0.0414 AC: 4678AN: 112968Hom.: 126 Cov.: 24 AF XY: 0.0392 AC XY: 1375AN XY: 35116
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Jul 15, 2018
GeneDx
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
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Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided
- -
Computational scores
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Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at