6-53499011-GT-G

Position:

• chr6-53499011-GT-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001498.4(GCLC):​c.1703-45del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 1,104,738 control chromosomes in the GnomAD database, including 6,093 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.11 (966 hom., cov: 30)
  • Exomes 𝑓: 0.10 (5127 hom.)
• Consequence: GCLC NM_001498.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0660

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]

GCLC-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 6-53499011-GT-G is Benign according to our data. Variant chr6-53499011-GT-G is described in ClinVar as [Benign]. Clinvar id is 1278849.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.14 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GCLC	NM_001498.4	c.1703-45del		intron_variant		ENST00000650454.1	NP_001489.1
GCLC-AS1	NR_183318.1	n.327-7133del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GCLC	ENST00000650454.1	c.1703-45del		intron_variant			NM_001498.4	ENSP00000497574	P1

Frequencies

GnomAD3 genomes AF: 0.112 AC: 16757 AN: 149634 Hom.: 964 Cov.: 30

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.0844

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.00838

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.0897

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.115

GnomAD3 exomes AF: 0.135 AC: 23961 AN: 177400 Hom.: 1319 AF XY: 0.141 AC XY: 13579 AN XY: 96322

Gnomad AFR exome AF: 0.158

Gnomad AMR exome AF: 0.0778

Gnomad ASJ exome AF: 0.159

Gnomad EAS exome AF: 0.0131

Gnomad SAS exome AF: 0.211

Gnomad FIN exome AF: 0.172

Gnomad NFE exome AF: 0.137

Gnomad OTH exome AF: 0.148

GnomAD4 exome AF: 0.102 AC: 97017 AN: 955004 Hom.: 5127 Cov.: 12 AF XY: 0.105 AC XY: 51815 AN XY: 492614

Gnomad4 AFR exome AF: 0.129

Gnomad4 AMR exome AF: 0.0615

Gnomad4 ASJ exome AF: 0.118

Gnomad4 EAS exome AF: 0.00612

Gnomad4 SAS exome AF: 0.155

Gnomad4 FIN exome AF: 0.141

Gnomad4 NFE exome AF: 0.0983

Gnomad4 OTH exome AF: 0.109

GnomAD4 genome AF: 0.112 AC: 16760 AN: 149734 Hom.: 966 Cov.: 30 AF XY: 0.112 AC XY: 8206 AN XY: 72980

Gnomad4 AFR AF: 0.133

Gnomad4 AMR AF: 0.0843

Gnomad4 ASJ AF: 0.105

Gnomad4 EAS AF: 0.00840

Gnomad4 SAS AF: 0.149

Gnomad4 FIN AF: 0.142

Gnomad4 NFE AF: 0.107

Gnomad4 OTH AF: 0.114

Bravo AF: 0.106

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

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: rs17880610; hg19: chr6-53363809;