6-53498689-GGGCT-G

Position:

• chr6-53498689-GGGCT-G

Variant summary

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

The NM_001498.4(GCLC):​c.*63_*66del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.485 in 981,478 control chromosomes in the GnomAD database, including 119,218 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.54 (23063 hom., cov: 0)
  • Exomes 𝑓: 0.48 (96155 hom.)
• Consequence: GCLC NM_001498.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.887

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 6-53498689-GGGCT-G is Benign according to our data. Variant chr6-53498689-GGGCT-G is described in ClinVar as [Benign]. Clinvar id is 1225691.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.696 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GCLC	NM_001498.4	c.*63_*66del		3_prime_UTR_variant	16/16	ENST00000650454.1	NP_001489.1
GCLC-AS1	NR_183318.1	n.327-7459_327-7456del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GCLC	ENST00000650454.1	c.*63_*66del		3_prime_UTR_variant	16/16		NM_001498.4	ENSP00000497574	P1

Frequencies

GnomAD3 genomes AF: 0.537 AC: 81262 AN: 151312 Hom.: 23024 Cov.: 0

Gnomad AFR AF: 0.703

Gnomad AMI AF: 0.411

Gnomad AMR AF: 0.612

Gnomad ASJ AF: 0.387

Gnomad EAS AF: 0.561

Gnomad SAS AF: 0.521

Gnomad FIN AF: 0.512

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.433

Gnomad OTH AF: 0.517

GnomAD4 exome AF: 0.476 AC: 395062 AN: 830048 Hom.: 96155 AF XY: 0.475 AC XY: 208006 AN XY: 438298

Gnomad4 AFR exome AF: 0.706

Gnomad4 AMR exome AF: 0.661

Gnomad4 ASJ exome AF: 0.406

Gnomad4 EAS exome AF: 0.617

Gnomad4 SAS exome AF: 0.513

Gnomad4 FIN exome AF: 0.508

Gnomad4 NFE exome AF: 0.436

Gnomad4 OTH exome AF: 0.482

GnomAD4 genome AF: 0.537 AC: 81364 AN: 151430 Hom.: 23063 Cov.: 0 AF XY: 0.542 AC XY: 40143 AN XY: 74044

Gnomad4 AFR AF: 0.703

Gnomad4 AMR AF: 0.612

Gnomad4 ASJ AF: 0.387

Gnomad4 EAS AF: 0.562

Gnomad4 SAS AF: 0.521

Gnomad4 FIN AF: 0.512

Gnomad4 NFE AF: 0.433

Gnomad4 OTH AF: 0.522

Alfa AF: 0.487 Hom.: 2284

Bravo AF: 0.553

Asia WGS AF: 0.545 AC: 1889 AN: 3474

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: rs1805189; hg19: chr6-53363487;