rs17883901

chr6-53545239-G-Achr6-53545239-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000616923.5(GCLC):c.-10+2817C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0637 in 154,512 control chromosomes in the GnomAD database, including 344 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.063 (337 hom., cov: 32)
  • Exomes 𝑓: 0.081 (7 hom.)
• Consequence: GCLC ENST00000616923.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2 O:1
• Conservation: PhyloP100: 0.743

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 6-53545239-G-A is Benign according to our data. Variant chr6-53545239-G-A is described in ClinVar as [Benign]. Clinvar id is 439753.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GCLC	ENST00000616923.5	c.-10+2817C>T		intron_variant		1
GCLC	ENST00000505197.1	c.-10+18878C>T		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.0635 AC: 9664 AN: 152180 Hom.: 337 Cov.: 32

Gnomad AFR AF: 0.0254

Gnomad AMI AF: 0.0833

Gnomad AMR AF: 0.0545

Gnomad ASJ AF: 0.100

Gnomad EAS AF: 0.124

Gnomad SAS AF: 0.0654

Gnomad FIN AF: 0.0625

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0813

Gnomad OTH AF: 0.0776

GnomAD4 exome AF: 0.0808 AC: 179 AN: 2216 Hom.: 7 AF XY: 0.0778 AC XY: 93 AN XY: 1196

Gnomad4 AFR exome AF: 0.0185

Gnomad4 AMR exome AF: 0.0313

Gnomad4 ASJ exome AF: 0.0694

Gnomad4 EAS exome AF: 0.159

Gnomad4 SAS exome AF: 0.0769

Gnomad4 FIN exome AF: 0.0615

Gnomad4 NFE exome AF: 0.0813

Gnomad4 OTH exome AF: 0.0379

GnomAD4 genome AF: 0.0634 AC: 9662 AN: 152296 Hom.: 337 Cov.: 32 AF XY: 0.0628 AC XY: 4677 AN XY: 74466

Gnomad4 AFR AF: 0.0253

Gnomad4 AMR AF: 0.0545

Gnomad4 ASJ AF: 0.100

Gnomad4 EAS AF: 0.124

Gnomad4 SAS AF: 0.0649

Gnomad4 FIN AF: 0.0625

Gnomad4 NFE AF: 0.0813

Gnomad4 OTH AF: 0.0791

Alfa AF: 0.0712 Hom.: 83

Bravo AF: 0.0622

Asia WGS AF: 0.106 AC: 369 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2 Other:1

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	This variant is associated with the following publications: (PMID: 21962117, 12598062) -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	May 10, 2022	- -

Myocardial infarction, susceptibility to Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Feb 19, 2003

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	13
Dann	Benign	0.83

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs17883901; hg19: chr6-53410037;