rs670548

Positions:

• chr6-53502191-C-T

Variant summary

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

The NM_001498.4(GCLC):​c.1396-1678G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.74 in 152,172 control chromosomes in the GnomAD database, including 43,052 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 0.74 (43052 hom., cov: 33)
• Consequence: GCLC NM_001498.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0350

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.919 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GCLC	NM_001498.4	c.1396-1678G>A		intron_variant		ENST00000650454.1	NP_001489.1
GCLC-AS1	NR_183318.1	n.327-3963C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GCLC	ENST00000650454.1	c.1396-1678G>A		intron_variant			NM_001498.4	ENSP00000497574	P1

Frequencies

GnomAD3 genomes AF: 0.740 AC: 112535 AN: 152054 Hom.: 42976 Cov.: 33

Gnomad AFR AF: 0.927

Gnomad AMI AF: 0.535

Gnomad AMR AF: 0.769

Gnomad ASJ AF: 0.579

Gnomad EAS AF: 0.734

Gnomad SAS AF: 0.821

Gnomad FIN AF: 0.712

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.631

Gnomad OTH AF: 0.707

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.740 AC: 112674 AN: 152172 Hom.: 43052 Cov.: 33 AF XY: 0.746 AC XY: 55487 AN XY: 74396

Gnomad4 AFR AF: 0.927

Gnomad4 AMR AF: 0.770

Gnomad4 ASJ AF: 0.579

Gnomad4 EAS AF: 0.734

Gnomad4 SAS AF: 0.822

Gnomad4 FIN AF: 0.712

Gnomad4 NFE AF: 0.631

Gnomad4 OTH AF: 0.711

Alfa AF: 0.664 Hom.: 32776

Bravo AF: 0.751

Asia WGS AF: 0.819 AC: 2846 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.4
DANN	Benign	0.77

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: rs670548; hg19: chr6-53366989;