rs2073420
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_001352514.2(HLCS):c.2122-30G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 1,394,790 control chromosomes in the GnomAD database, including 147,121 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.41 ( 13405 hom., cov: 32)
Exomes 𝑓: 0.46 ( 133716 hom. )
Consequence
HLCS
NM_001352514.2 intron
NM_001352514.2 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.115
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 -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
Variant 21-36759871-C-T is Benign according to our data. Variant chr21-36759871-C-T is described in ClinVar as [Benign]. Clinvar id is 256035.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.529 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
HLCS | NM_001352514.2 | c.2122-30G>A | intron_variant | ENST00000674895.3 | NP_001339443.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
HLCS | ENST00000674895.3 | c.2122-30G>A | intron_variant | NM_001352514.2 | ENSP00000502087.2 |
Frequencies
GnomAD3 genomes AF: 0.414 AC: 62817AN: 151836Hom.: 13404 Cov.: 32
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GnomAD3 exomes AF: 0.431 AC: 108284AN: 251052Hom.: 24149 AF XY: 0.444 AC XY: 60350AN XY: 135794
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GnomAD4 exome AF: 0.460 AC: 572297AN: 1242836Hom.: 133716 Cov.: 18 AF XY: 0.466 AC XY: 293232AN XY: 629918
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GnomAD4 genome AF: 0.413 AC: 62821AN: 151954Hom.: 13405 Cov.: 32 AF XY: 0.412 AC XY: 30567AN XY: 74272
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ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 14, 2018 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Holocarboxylase synthetase deficiency Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jun 10, 2021 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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