rs7515191
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_002061.4(GCLM):c.277+44C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.361 in 975,892 control chromosomes in the GnomAD database, including 69,074 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.44 ( 16906 hom., cov: 32)
Exomes 𝑓: 0.35 ( 52168 hom. )
Consequence
GCLM
NM_002061.4 intron
NM_002061.4 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.0810
Genes affected
GCLM (HGNC:4312): (glutamate-cysteine ligase modifier 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. Gamma glutamylcysteine synthetase deficiency has been implicated in some forms of hemolytic anemia. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Apr 2015]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.675 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GCLM | NM_002061.4 | c.277+44C>T | intron_variant | ENST00000370238.8 | |||
GCLM | NM_001308253.2 | c.211+44C>T | intron_variant | ||||
GCLM | XM_011541261.3 | c.13+44C>T | intron_variant | ||||
GCLM | XM_047418031.1 | c.277+44C>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GCLM | ENST00000370238.8 | c.277+44C>T | intron_variant | 1 | NM_002061.4 | P1 | |||
GCLM | ENST00000615724.1 | c.211+44C>T | intron_variant | 1 | |||||
GCLM | ENST00000467772.1 | n.277+44C>T | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.445 AC: 67509AN: 151840Hom.: 16871 Cov.: 32
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GnomAD3 exomes AF: 0.362 AC: 82965AN: 229424Hom.: 16583 AF XY: 0.348 AC XY: 43332AN XY: 124528
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GnomAD4 exome AF: 0.346 AC: 284685AN: 823934Hom.: 52168 Cov.: 11 AF XY: 0.339 AC XY: 147705AN XY: 435296
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GnomAD4 genome ? AF: 0.445 AC: 67600AN: 151958Hom.: 16906 Cov.: 32 AF XY: 0.442 AC XY: 32844AN XY: 74284
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ClinVar
Not reported inComputational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at