rs542914

Variant names:

• chr6-53511850-C-A
• rs542914
• NM_001498.4:c.753+2354G>T

Your query was ambiguous. Multiple possible variants found:

• chr6-53511850-C-A
• chr6-53511850-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.753+2354G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.36 (7747 hom., cov: 17)
• Consequence: GCLC NM_001498.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.268

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.388 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GCLC	NM_001498.4	c.753+2354G>T		intron_variant	Intron 6 of 15	ENST00000650454.1	NP_001489.1
GCLC	NM_001197115.2	c.639+2354G>T		intron_variant	Intron 5 of 14		NP_001184044.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GCLC	ENST00000650454.1	c.753+2354G>T		intron_variant	Intron 6 of 15		NM_001498.4	ENSP00000497574.1

Frequencies

GnomAD3 genomes AF: 0.362 AC: 43048 AN: 119010 Hom.: 7746 Cov.: 17

Gnomad AFR AF: 0.349

Gnomad AMI AF: 0.240

Gnomad AMR AF: 0.313

Gnomad ASJ AF: 0.338

Gnomad EAS AF: 0.149

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.418

Gnomad MID AF: 0.388

Gnomad NFE AF: 0.392

Gnomad OTH AF: 0.354

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

GnomAD4 genome AF: 0.362 AC: 43047 AN: 119034 Hom.: 7747 Cov.: 17 AF XY: 0.360 AC XY: 19690 AN XY: 54746

Gnomad4 AFR AF: 0.349

Gnomad4 AMR AF: 0.313

Gnomad4 ASJ AF: 0.338

Gnomad4 EAS AF: 0.149

Gnomad4 SAS AF: 0.242

Gnomad4 FIN AF: 0.418

Gnomad4 NFE AF: 0.392

Gnomad4 OTH AF: 0.354

Alfa AF: 0.279 Hom.: 881

Bravo AF: 0.335

Asia WGS AF: 0.212 AC: 737 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.3
DANN	Benign	0.57

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: rs542914; hg19: chr6-53376648;