6-53507347-T-C

Position:

• chr6-53507347-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001498.4(GCLC):​c.1084+133A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 854,782 control chromosomes in the GnomAD database, including 16,584 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.18 (3779 hom., cov: 32)
  • Exomes 𝑓: 0.14 (12805 hom.)
• Consequence: GCLC NM_001498.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0690

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:56649): (GCLC antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 6-53507347-T-C is Benign according to our data. Variant chr6-53507347-T-C is described in ClinVar as [Benign]. Clinvar id is 1261932.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.423 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GCLC	NM_001498.4	c.1084+133A>G		intron_variant		ENST00000650454.1
GCLC	NM_001197115.2	c.970+133A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GCLC	ENST00000650454.1	c.1084+133A>G		intron_variant			NM_001498.4	P1
GCLC-AS1	ENST00000655377.1	n.1042T>C		non_coding_transcript_exon_variant	3/3

Frequencies

GnomAD3 genomes AF: 0.184 AC: 27976 AN: 151956 Hom.: 3761 Cov.: 32

Gnomad AFR AF: 0.283

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.361

Gnomad ASJ AF: 0.0919

Gnomad EAS AF: 0.437

Gnomad SAS AF: 0.236

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.0800

Gnomad OTH AF: 0.176

GnomAD4 exome AF: 0.142 AC: 99818 AN: 702706 Hom.: 12805 AF XY: 0.141 AC XY: 53023 AN XY: 375436

Gnomad4 AFR exome AF: 0.286

Gnomad4 AMR exome AF: 0.491

Gnomad4 ASJ exome AF: 0.103

Gnomad4 EAS exome AF: 0.451

Gnomad4 SAS exome AF: 0.219

Gnomad4 FIN exome AF: 0.0990

Gnomad4 NFE exome AF: 0.0795

Gnomad4 OTH exome AF: 0.150

GnomAD4 genome AF: 0.184 AC: 28048 AN: 152076 Hom.: 3779 Cov.: 32 AF XY: 0.192 AC XY: 14247 AN XY: 74330

Gnomad4 AFR AF: 0.283

Gnomad4 AMR AF: 0.362

Gnomad4 ASJ AF: 0.0919

Gnomad4 EAS AF: 0.438

Gnomad4 SAS AF: 0.237

Gnomad4 FIN AF: 0.101

Gnomad4 NFE AF: 0.0800

Gnomad4 OTH AF: 0.181

Alfa AF: 0.134 Hom.: 1119

Bravo AF: 0.211

Asia WGS AF: 0.311 AC: 1078 AN: 3478

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

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	13
DANN	Benign	0.78

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: rs1555903; hg19: chr6-53372145;