21-36930243-CA-C
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1
The NM_001352514.2(HLCS):c.1620+7del variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 1,613,368 control chromosomes in the GnomAD database, including 25,229 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.13 ( 1587 hom., cov: 30)
Exomes 𝑓: 0.17 ( 23642 hom. )
Consequence
HLCS
NM_001352514.2 splice_region, intron
NM_001352514.2 splice_region, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.51
Genes affected
HLCS (HGNC:4976): (holocarboxylase synthetase) This gene encodes an enzyme that catalyzes the binding of biotin to carboxylases and histones. The protein plays an important role in gluconeogenesis, fatty acid synthesis and branched chain amino acid catabolism. Defects in this gene are the cause of holocarboxylase synthetase deficiency. Multiple alternatively spliced variants, encoding the same protein, have been identified.[provided by RefSeq, Jun 2011]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP6
Variant 21-36930243-CA-C is Benign according to our data. Variant chr21-36930243-CA-C is described in ClinVar as [Likely_benign]. Clinvar id is 92915.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-36930243-CA-C is described in Lovd as [Benign]. Variant chr21-36930243-CA-C is described in Lovd as [Likely_benign].
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
HLCS | NM_001352514.2 | c.1620+7del | splice_region_variant, intron_variant | ENST00000674895.3 | NP_001339443.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
HLCS | ENST00000674895.3 | c.1620+7del | splice_region_variant, intron_variant | NM_001352514.2 | ENSP00000502087 | P4 |
Frequencies
GnomAD3 genomes AF: 0.126 AC: 19232AN: 152114Hom.: 1588 Cov.: 30
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GnomAD3 exomes AF: 0.134 AC: 33730AN: 251328Hom.: 2875 AF XY: 0.138 AC XY: 18686AN XY: 135840
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GnomAD4 exome AF: 0.173 AC: 252293AN: 1461136Hom.: 23642 Cov.: 30 AF XY: 0.171 AC XY: 124155AN XY: 726882
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GnomAD4 genome AF: 0.126 AC: 19227AN: 152232Hom.: 1587 Cov.: 30 AF XY: 0.123 AC XY: 9184AN XY: 74432
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:8
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jan 16, 2013 | - - |
Holocarboxylase synthetase deficiency Benign:3
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 01, 2024 | - - |
not provided Benign:2
Likely benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 11, 2018 | - - |
Computational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at