rs636933

chr6-53513279-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000514004.5(GCLC):c.*919C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 152,272 control chromosomes in the GnomAD database, including 3,126 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 0.20 (3124 hom., cov: 33)
  • Exomes 𝑓: 0.12 (2 hom.)
• Consequence: GCLC ENST00000514004.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.949

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.233 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GCLC	NM_001498.4	c.753+925C>T		intron_variant		ENST00000650454.1
GCLC	NM_001197115.2	c.639+925C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GCLC	ENST00000650454.1	c.753+925C>T		intron_variant			NM_001498.4	P1

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30385 AN: 152062 Hom.: 3122 Cov.: 33

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.182

Gnomad EAS AF: 0.139

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.241

Gnomad MID AF: 0.172

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.194

GnomAD4 exome AF: 0.120 AC: 11 AN: 92 Hom.: 2 Cov.: 0 AF XY: 0.0625 AC XY: 4 AN XY: 64

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.125

Gnomad4 NFE exome AF: 0.155

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.200 AC: 30384 AN: 152180 Hom.: 3124 Cov.: 33 AF XY: 0.197 AC XY: 14643 AN XY: 74414

Gnomad4 AFR AF: 0.168

Gnomad4 AMR AF: 0.143

Gnomad4 ASJ AF: 0.182

Gnomad4 EAS AF: 0.139

Gnomad4 SAS AF: 0.136

Gnomad4 FIN AF: 0.241

Gnomad4 NFE AF: 0.237

Gnomad4 OTH AF: 0.194

Alfa AF: 0.223 Hom.: 641

Bravo AF: 0.192

Asia WGS AF: 0.129 AC: 450 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	1.0
Dann	Benign	0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs636933; hg19: chr6-53378077;