rs2073421
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_001352514.2(HLCS):c.1893-46G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.54 in 1,580,300 control chromosomes in the GnomAD database, including 233,087 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.59 ( 26905 hom., cov: 31)
Exomes 𝑓: 0.53 ( 206182 hom. )
Consequence
HLCS
NM_001352514.2 intron
NM_001352514.2 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.208
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=-0.9).
BP6
?
Variant 21-36767331-C-A is Benign according to our data. Variant chr21-36767331-C-A is described in ClinVar as [Benign]. Clinvar id is 256034.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.689 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HLCS | NM_001352514.2 | c.1893-46G>T | intron_variant | ENST00000674895.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HLCS | ENST00000674895.3 | c.1893-46G>T | intron_variant | NM_001352514.2 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.589 AC: 89404AN: 151846Hom.: 26847 Cov.: 31
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GnomAD3 exomes AF: 0.568 AC: 142613AN: 251048Hom.: 41302 AF XY: 0.555 AC XY: 75365AN XY: 135704
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GnomAD4 exome AF: 0.534 AC: 763109AN: 1428336Hom.: 206182 Cov.: 25 AF XY: 0.531 AC XY: 378170AN XY: 712602
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GnomAD4 genome ? AF: 0.589 AC: 89519AN: 151964Hom.: 26905 Cov.: 31 AF XY: 0.592 AC XY: 43955AN XY: 74300
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
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 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
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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