X-53422829-C-T

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

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.333
Variant links:
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
SMC1ANM_006306.4 linkc.-229G>A upstream_gene_variant ENST00000322213.9 NP_006297.2 Q14683A0A384MR33Q68EN4
RIBC1NM_001031745.5 linkc.-265C>T upstream_gene_variant ENST00000375327.6 NP_001026915.1 Q8N443-1A0A024R9X7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SMC1AENST00000322213.9 linkc.-229G>A upstream_gene_variant 1 NM_006306.4 ENSP00000323421.3 Q14683
RIBC1ENST00000375327.6 linkc.-265C>T upstream_gene_variant 1 NM_001031745.5 ENSP00000364476.3 Q8N443-1

Frequencies

GnomAD3 genomes
AF:
0.0414
AC:
4680
AN:
112917
Hom.:
126
Cov.:
24
AF XY:
0.0393
AC XY:
1376
AN XY:
35055
show subpopulations
Gnomad AFR
AF:
0.00880
Gnomad AMI
AF:
0.160
Gnomad AMR
AF:
0.0261
Gnomad ASJ
AF:
0.0226
Gnomad EAS
AF:
0.00112
Gnomad SAS
AF:
0.00610
Gnomad FIN
AF:
0.0637
Gnomad MID
AF:
0.0167
Gnomad NFE
AF:
0.0653
Gnomad OTH
AF:
0.0361
GnomAD4 exome
AF:
0.0488
AC:
12179
AN:
249318
Hom.:
279
Cov.:
0
AF XY:
0.0457
AC XY:
3426
AN XY:
74946
show subpopulations
Gnomad4 AFR exome
AF:
0.00946
Gnomad4 AMR exome
AF:
0.0216
Gnomad4 ASJ exome
AF:
0.0250
Gnomad4 EAS exome
AF:
0.0000630
Gnomad4 SAS exome
AF:
0.00776
Gnomad4 FIN exome
AF:
0.0611
Gnomad4 NFE exome
AF:
0.0665
Gnomad4 OTH exome
AF:
0.0476
GnomAD4 genome
AF:
0.0414
AC:
4678
AN:
112968
Hom.:
126
Cov.:
24
AF XY:
0.0392
AC XY:
1375
AN XY:
35116
show subpopulations
Gnomad4 AFR
AF:
0.00878
Gnomad4 AMR
AF:
0.0260
Gnomad4 ASJ
AF:
0.0226
Gnomad4 EAS
AF:
0.00112
Gnomad4 SAS
AF:
0.00611
Gnomad4 FIN
AF:
0.0637
Gnomad4 NFE
AF:
0.0652
Gnomad4 OTH
AF:
0.0357
Alfa
AF:
0.0482
Hom.:
267
Bravo
AF:
0.0389

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

- -

-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.76
CADD
Benign
4.8
DANN
Benign
0.89

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs186837286; hg19: chrX-53449778; API