chr14-87950751-GA-G
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1
The NM_000153.4(GALC):c.1162-4del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.96 ( 69014 hom., cov: 0)
Exomes 𝑓: 0.97 ( 530192 hom. )
Consequence
GALC
NM_000153.4 splice_region, splice_polypyrimidine_tract, intron
NM_000153.4 splice_region, splice_polypyrimidine_tract, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.150
Genes affected
GALC (HGNC:4115): (galactosylceramidase) This gene encodes a lysosomal protein which hydrolyzes the galactose ester bonds of galactosylceramide, galactosylsphingosine, lactosylceramide, and monogalactosyldiglyceride. Mutations in this gene have been associated with Krabbe disease, also known as globoid cell leukodystrophy. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP6
Variant 14-87950751-GA-G is Benign according to our data. Variant chr14-87950751-GA-G is described in ClinVar as [Benign]. Clinvar id is 92493.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-87950751-GA-G is described in Lovd as [Pathogenic]. Variant chr14-87950751-GA-G is described in Lovd as [Benign]. Variant chr14-87950751-GA-G is described in Lovd as [Likely_benign].
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GALC | NM_000153.4 | c.1162-4del | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000261304.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GALC | ENST00000261304.7 | c.1162-4del | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_000153.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.959 AC: 143279AN: 149400Hom.: 68984 Cov.: 0
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GnomAD3 exomes AF: 0.974 AC: 207143AN: 212618Hom.: 100902 AF XY: 0.977 AC XY: 112939AN XY: 115542
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GnomAD4 exome AF: 0.967 AC: 1097368AN: 1134968Hom.: 530192 Cov.: 0 AF XY: 0.969 AC XY: 554172AN XY: 572076
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GnomAD4 genome AF: 0.959 AC: 143367AN: 149512Hom.: 69014 Cov.: 0 AF XY: 0.961 AC XY: 69986AN XY: 72826
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ClinVar
Significance: Benign
Submissions summary: Pathogenic:1Benign:15
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:5
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Aug 01, 2014 | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Galactosylceramide beta-galactosidase deficiency Benign:5
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | May 12, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Benign, criteria provided, single submitter | clinical testing | Molecular Genetics, Royal Melbourne Hospital | May 04, 2023 | European Non-Finnish population allele frequency is 97.92% (rs751373579, 109,537/111,048 alleles, 54,014 homozygotes in gnomAD v2.1). Based on the classification scheme RMH Modified ACMG/AMP Guidelines v1.2.1, this variant is classified as BENIGN. Following criteria are met: BA1 - |
not provided Benign:4
Likely benign, no assertion criteria provided | clinical testing | Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) | - | - - |
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | May 16, 2016 | Variant summary: The GALC c.1162-4delT variant involves the alteration of a non-conserved intronic nucleotide. One in silico tool predicts a polymorphism outcome for this variant. This variant was found in 104106/106498 control chromosomes (50900 homozygotes) at a frequency of 0.9775395, which is approximately 437 times the estimated maximal expected allele frequency of a pathogenic GALC variant (0.0022361), suggesting this variant is likely a benign polymorphism and the major allele in general population. In addition, one clinical diagnostic laboratory classified this variant as benign. Taken together, this variant is classified as benign. - |
Benign, no assertion criteria provided | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Oct 21, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 24, 2018 | - - |
Abnormal brain morphology Pathogenic:1
Likely pathogenic, flagged submission | research | Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine | - | - - |
GALC-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 06, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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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