rs1014852
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_001498.4(GCLC):c.1198-59T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 920,932 control chromosomes in the GnomAD database, including 19,115 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.19 ( 4576 hom., cov: 32)
Exomes 𝑓: 0.13 ( 14539 hom. )
Consequence
GCLC
NM_001498.4 intron
NM_001498.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.80
Genes affected
GCLC (HGNC:4311): (glutamate-cysteine ligase catalytic subunit) Glutamate-cysteine ligase, also known as gamma-glutamylcysteine synthetase is the first rate-limiting enzyme of glutathione synthesis. The enzyme consists of two subunits, a heavy catalytic subunit and a light regulatory subunit. This locus encodes the catalytic subunit, while the regulatory subunit is derived from a different gene located on chromosome 1p22-p21. Mutations at this locus have been associated with hemolytic anemia due to deficiency of gamma-glutamylcysteine synthetase and susceptibility to myocardial infarction.[provided by RefSeq, Oct 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
?
Variant 6-53505954-A-T is Benign according to our data. Variant chr6-53505954-A-T is described in ClinVar as [Benign]. Clinvar id is 1251336.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GCLC | NM_001498.4 | c.1198-59T>A | intron_variant | ENST00000650454.1 | |||
GCLC-AS1 | NR_183318.1 | n.327-200A>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GCLC | ENST00000650454.1 | c.1198-59T>A | intron_variant | NM_001498.4 | P1 | ||||
GCLC-AS1 | ENST00000655377.1 | n.212-200A>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.192 AC: 29194AN: 152042Hom.: 4554 Cov.: 32
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GnomAD4 exome AF: 0.133 AC: 102023AN: 768772Hom.: 14539 Cov.: 10 AF XY: 0.130 AC XY: 53268AN XY: 410038
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GnomAD4 genome ? AF: 0.192 AC: 29276AN: 152160Hom.: 4576 Cov.: 32 AF XY: 0.199 AC XY: 14817AN XY: 74378
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 18, 2021 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at