rs1264011
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_006306.4(SMC1A):c.-19C>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 0.435 in 112,256 control chromosomes in the GnomAD database, including 9,273 homozygotes. There are 14,999 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.43 ( 9273 hom., 14999 hem., cov: 25)
Exomes 𝑓: 0.57 ( 115090 hom. 174600 hem. )
Failed GnomAD Quality Control
Consequence
SMC1A
NM_006306.4 5_prime_UTR
NM_006306.4 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.251
Genes affected
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=-0.71).
BP6
Variant X-53422619-G-A is Benign according to our data. Variant chrX-53422619-G-A is described in ClinVar as [Benign]. Clinvar id is 95364.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-53422619-G-A is described in Lovd as [Benign]. Variant chrX-53422619-G-A is described in Lovd as [Likely_benign].
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.587 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SMC1A | NM_006306.4 | c.-19C>T | 5_prime_UTR_variant | 1/25 | ENST00000322213.9 | ||
SMC1A | NM_001281463.1 | c.-231C>T | 5_prime_UTR_variant | 1/26 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMC1A | ENST00000322213.9 | c.-19C>T | 5_prime_UTR_variant | 1/25 | 1 | NM_006306.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.435 AC: 48816AN: 112202Hom.: 9278 Cov.: 25 AF XY: 0.436 AC XY: 14989AN XY: 34412
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GnomAD3 exomes AF: 0.523 AC: 94446AN: 180723Hom.: 16594 AF XY: 0.532 AC XY: 34869AN XY: 65599
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GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.573 AC: 572950AN: 1000785Hom.: 115090 Cov.: 18 AF XY: 0.595 AC XY: 174600AN XY: 293349
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Data not reliable, filtered out with message: InbreedingCoeff
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GnomAD4 genome AF: 0.435 AC: 48818AN: 112256Hom.: 9273 Cov.: 25 AF XY: 0.435 AC XY: 14999AN XY: 34476
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ClinVar
Significance: Benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Aug 18, 2014 | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan | Jul 15, 2024 | This variant is classified as Benign based on local population frequency. This variant was detected in 38% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 35. Only high quality variants are reported. - |
Developmental and epileptic encephalopathy, 85, with or without midline brain defects Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 15, 2021 | - - |
Congenital muscular hypertrophy-cerebral syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 15, 2021 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
De Lange syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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