chr6-53513036-C-T

Position:

• chr6-53513036-C-T

Variant summary

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

The ENST00000514004.5(GCLC):​c.*1162G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.444 in 152,078 control chromosomes in the GnomAD database, including 15,380 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 0.44 (15380 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: GCLC ENST00000514004.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• 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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.56 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GCLC	NM_001498.4	c.753+1168G>A		intron_variant		ENST00000650454.1	NP_001489.1
GCLC	NM_001197115.2	c.639+1168G>A		intron_variant			NP_001184044.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GCLC	ENST00000650454.1	c.753+1168G>A		intron_variant			NM_001498.4	ENSP00000497574.1

Frequencies

GnomAD3 genomes AF: 0.444 AC: 67457 AN: 151960 Hom.: 15367 Cov.: 33

Gnomad AFR AF: 0.360

Gnomad AMI AF: 0.443

Gnomad AMR AF: 0.570

Gnomad ASJ AF: 0.393

Gnomad EAS AF: 0.403

Gnomad SAS AF: 0.522

Gnomad FIN AF: 0.452

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.465

Gnomad OTH AF: 0.452

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.444 AC: 67492 AN: 152078 Hom.: 15380 Cov.: 33 AF XY: 0.447 AC XY: 33219 AN XY: 74340

Gnomad4 AFR AF: 0.359

Gnomad4 AMR AF: 0.570

Gnomad4 ASJ AF: 0.393

Gnomad4 EAS AF: 0.404

Gnomad4 SAS AF: 0.523

Gnomad4 FIN AF: 0.452

Gnomad4 NFE AF: 0.465

Gnomad4 OTH AF: 0.456

Alfa AF: 0.465 Hom.: 33387

Bravo AF: 0.448

Asia WGS AF: 0.464 AC: 1615 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.6
DANN	Benign	0.53

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: rs574389; hg19: chr6-53377834;